Therapeutic Interventions for Accelerated Trials/Application in Long Covid

Long Covid Action Project’s ACT NOW Treatment Campaign

Finalized by Long Covid Action Project CURE Committee, January 20, 2025

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Antiviral Drugs | Biologics  | Other Drugs of Interest

Action Item: Deadline Originally Feb, 1 — now extended

Instructions: Use the form fields provided for each drug treatment to submit information about suggested treatments to the NIH Recover-TLC Information Request Form.  This list currently has 17 antivirals, 14 monoclonal antibodies,  and 18 other drugs of interest for a total of 49 drug treatments.

Biomarkers Form (this is a separate link from the RECOVER-TLC form) here’s what we’ve added for the mandated parts of the form:

PDF download of the ACT NOW treatment list. This list is also provided below on this web page starting with “Antiviral Drugs.”

After filling out the NIH form sign the LCAP action letter to NIH »

Antiviral Drugs

• Abacavir (Ziagen) – nucleoside analog reverse transcriptase inhibitor. Recommended uses would be in combination therapeutics. ✓

NIH Form

Name of intervention: Abacavir (Ziagen)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

If approved, current indication: Other

Symptoms/Syndromes intervention aims to target: SARS-CoV-2 viral persistence

URLs:

Copertino 2020 https://www.tandfonline.com/doi/full/10.1080/07391102.2021.1901144

Alavian 2020 https://pmc.ncbi.nlm.nih.gov/articles/PMC7753707/

Tomic 2021 https://www.sciencedirect.com/science/article/pii/S2352914821000198

• Atazanavir (Reyataz) – Biomed’s azapeptide antiretroviral protease inhibitor used to treat HIV AIDS infection; inhibits the enzyme UDP glucuronosyltransferase (UGT) 1A1 ✓

NIH Form

Name of intervention: Atazanavir (Reyataz)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: inhibit the viral replication cycle of SARS-CoV-2  by binding the main protease inhibitor

Clinical data for an acute COVID-19 indication:  RCT

Acute COVID-19 study status: Completed

URLs:

Brazil Clinical Trial 2021 https://clinicaltrials.gov/study/NCT04468087

Biomed Clinical Trial 2022 https://clinicaltrials.gov/study/NCT04452565   Copertino  Jr. 2021 https://www.tandfonline.com/doi/full/10.1080/07391102.2021.1901144#d1e392

• Azvudine – Chinese antiviral used in acute COVID. Nucleoside analog inhibitor of RdRp. ✓

Select Articles/Clinical Trials:

Azvudine versus Paxlovid for oral treatment of COVID-19 in Chinese patients with pre-existing comorbidities (May 2023) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188372/

Azvudine versus Paxlovid for oral treatment of COVID-19 in Chinese patients with pre-existing comorbidities (Jan 2024)

https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08944-z

Efficacy and safety of azvudine in patients with COVID-19: A systematic review and meta-analysis (Sep 2023)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10559905/

NIH Form

Name of intervention: Azvudine

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: Reduction of SARS-CoV-2 viral load

Clinical data for an acute COVID-19 indication: Retrospective cohort studies

Acute COVID-19 study status: Completed

URLs:

Phase 3 Clinical Trial 2022 https://clinicaltrials.gov/study/NCT05033145

Phase 3 Clinical Trial 2021 https://clinicaltrials.gov/study/NCT04668235

Dian 2023 https://pmc.ncbi.nlm.nih.gov/articles/PMC10188372/

Zhou 2024 https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08944-z

Chen 2023 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10559905/

• Dolutegravir (Tivicay/GSK-572/S-349572) –  ViiV Healthcare’s antiretroviral integrase inhibitor. ✓

NIH Form

Name of intervention: Dolutegravir (Tivicay/GSK-572)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: increase CD4+ T cell count

URLs:

Erukainure, 2024 https://pmc.ncbi.nlm.nih.gov/articles/PMC11626820/

Buzon 2023  https://pmc.ncbi.nlm.nih.gov/articles/PMC9963008/

• Ensitrelvir (Xocova S-217622) – Shionogi’s antiviral post-exposure prophylaxis for acute COVID. 3CL protease inhibitor. ✓

NIH Form

Name of intervention: Ensitrelvir (Xocova S-217622)

Type of therapeutic intervention: Drug

Stage of overall development: Phase 2

Symptoms/Syndromes intervention aims to target: Reduction of SARS-CoV-2 viral load; inflammation

Clinical data for a long COVID-19 indication: RCT

Long COVID-19 study status: Ongoing

URLs:

UCSF Clinical Trial https://clinicaltrials.gov/study/NCT06161688

Yotsuyanagi Sep 2024 https://www.sciencedirect.com/science/article/pii/S0166354224001670

Yotsuyanagi Feb 2024 https://europepmc.org/article/MED/38335000

Yamato 2024 https://pubmed.ncbi.nlm.nih.gov/38367932/

• Ibuzatrelvir (PF-07817883) – Pfizer’s oral SARS-CoV-2 main protease (Mpro) inhibitor ✓

NIH Form

Name of intervention: Ibuzatrelvir (PF-07817883)

Type of therapeutic intervention: Drug

Stage of overall development: Phase 2/3

Symptoms/Syndromes intervention aims to target: Reduction of SARS-CoV-2 viral load and inhibiting SARS-CoV-2 viral replication.

Clinical data for Acute COVID-19 indication: RCT

Acute COVID-19 study status: Ongoing

URLs:

Pfizer Phase 3 Clinical Trial https://clinicaltrials.gov/study/NCT06679140    Mortezavi 2024 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciae529/7863440

Brewitz 2024 https://pubmed.ncbi.nlm.nih.gov/38967233/

Pfizer Phase 2b Clinical Trial https://pfizermedical.pfizerpro.com/api/vc/en/medical/assets/0f98ccb4-08bb-46d6-abfe-3a89b62dc8fc/Ibuzatrelvir%20Phase%202b%20Study%20results-updated%20poster%20%281%29.pdf

• Indinavir (Crixivan) – Merck’s small molecule antiretroviral protease inhibitor used to treat HIV AIDS  ✓

NIH Form

Name of intervention:Indinavir (Crixivan)

Type of therapeutic intervention: Drug

Stage of overall development:  Approved for another indication

Symptoms/Syndromes intervention aims to target: reduce viral load and inhibit  the viral replication cycle of SARS-CoV-2  by binding the main protease inhibitor.

URLs:

Indu et al., 2020 https://pmc.ncbi.nlm.nih.gov/articles/PMC7587076/

Copertino  Jr. 2021 https://www.tandfonline.com/doi/full/10.1080/07391102.2021.1901144#d1e392

• Lenacapavir (Sunlenca) – Gilead antiretroviral for HIV/AIDS that rigidifies HIV’s capsid protein protecting the virus’s RNA, which blocks transmission of the virus. May have potential against other viruses such as SARS-CoV-2 (even the prevention or reduction of reinfections would help people with Long Covid. This drug is hailed as the discovery of the year for treating HIV. (Cautionary note: computer modeling study raised a question of respiratory toxicity and non-genotoxic carcinogenicity) ✓

NIH Form

Name of intervention: Lenacapavir (Sunlenca)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: Reduction of SARS-CoV-2 viral load; reduction of SARS-CoV-2 reinfection potential

URLs:

Erukainure 2024 https://pmc.ncbi.nlm.nih.gov/articles/PMC11626820/

Kelley 2024 https://www.nejm.org/doi/full/10.1056/NEJMoa2411858

• Maraviroc (Selzentry) – Chemokine receptor (CCR5) antagonist that acts against HIV by blocking cellular entry. Has been used in Long Covid protocols, with demonstrated clinical improvements. ✓

NIH Form

Name of intervention: Maraviroc (Selzentry)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: SARS-CoV-2 viral persistence

Clinical data for a long COVID-19 indication: Randomized parallel assignment quadruple blinded

Long COVID-19 study status: Ongoing

URLs:

Mt Sinai Clinical Trial 2024 https://clinicaltrials.gov/study/NCT06511063

Patterson 2023 https://pubmed.ncbi.nlm.nih.gov/36844201/

• Obeldesivir (GS-5245/ATV006) – Gilead’s small molecule oral antiviral (an oral remdesivir analogue) ✓

NIH Form

Name of intervention: Obeldesivir – (GS-5245/ATV006)

Type of therapeutic intervention: Drug

Stage of overall development: Phase 3

Symptoms/Syndromes intervention aims to target: Reduction of SARS-CoV-2 viral RNA and inhibiting SARS-CoV-2 replication.

Clinical data for Acute COVID-19 indication: Double-blinded RCT

Acute COVID-19 study status: Completed

URLs:

Gilead OAKTREE trial 2024 https://clinicaltrials.gov/study/NCT05715528  Gilead BIRCH clinical trial 2024 https://clinicaltrials.gov/study/NCT05603143   UNC 2024 https://sph.unc.edu/sph-news/oral-nucleoside-antiviral-is-progressing-toward-future-pandemic-preparedness/

Gilead 2024 https://www.askgileadmedical.com/docs/conference/2024_IDWeek_COVID_ODV_P92_Rodriguez_BIRCHTiterOral_FINAL@pdf

• Sofosbuvir and its various combination formulations (e.g., ledipasvir-sofosbuvir [Harvoni]) – Hepatitis C antiviral with demonstrated effectiveness against acute COVID. Nucleotide analog inhibitor RdRp with stronger binding affinity for SARS-CoV-2 RdRp than tenofovir. Additionally, novel derivatives of sofosbuvir should be tested as several have been shown to have even stronger binding affinity for SARS-CoV-2. ✓

NIH Form

Name of intervention: Sofosbuvir and its various combination formulations (e.g., ledipasvir-sofosbuvir [Harvoni]; sofosbuvir-daclatasvir; sofosbuvir-ravidasvir)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: SARS-CoV-2 viral persistence

Clinical data for a COVID-19 indication: Single-blinded parallel RCT

COVID-19 study status: Completed

URLs:

Elgohary 2022 https://pmc.ncbi.nlm.nih.gov/articles/PMC9015168/

Alrehaily 2023 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10754943/

Hsu 2022 https://pmc.ncbi.nlm.nih.gov/articles/PMC8817946/

Abbass 2022 https://pubmed.ncbi.nlm.nih.gov/34379337/

• S-892216 – Shionogi 3CL protease inhibitor developed through the Rapid Response Partnership Vehicle (RRPV) under the Biomedical Advanced Research and Development Authority (BARDA) as a pre-exposure prophylactic for COVID-19. ✓

NIH Form

Name of intervention: S-892216

Type of therapeutic intervention: Drug

Stage of overall development: Preclinical

Symptoms/Syndromes intervention aims to target: Reduction of SARS-CoV-2 viral load by blocking the main protease (Mpro) of the SARS-CoV-2 virus, preventing its replication within cells; reduction of SARS-CoV-2 reinfection potential

URLs:

Pharmaceutical Technology 2025 https://www.pharmaceutical-technology.com/news/shionogi-awarded-375m-from-hhs-for-preventative-covid-19-injectable/

Clinical Trial Vanguard 2025 https://www.clinicaltrialvanguard.com/news/shionogis-s-892216-breakthrough-covid-19-antiviral-for-at-risk-groups/

• STRIBILD (elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate) – an antiretroviral combination therapy used as post-exposure prophylaxis for HIV and for treatment of HIV. Also effective against EBV reactivation and Hepatitis B. STRIBILD contains the drugs in Truvada plus cobicistat (a booster that increases levels of antivirals in the body) and elvitegravir (an integrase inhibitor). ✓

NIH Form

Name of intervention: STRIBILD (elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: SARS-CoV-2 viral persistence

Clinical data for a long COVID-19 indication: Randomized parallel assignment quadruple blinded

Long COVID-19 study status: Ongoing

URLs:

Mt Sinai 2024 https://clinicaltrials.gov/study/NCT06511063

UCSF 2022 https://pmc.ncbi.nlm.nih.gov/articles/PMC8243808/#:~:text=PWH%20taking%20ART.-,1,supporting%20the%20possibility%20of%20confounding

Luca Shytaj 2022 https://outbreak.info/resources/pmid35229634

AAAS 2023 https://www.eurekalert.org/news-releases/1010145

ISS Italy 2022 https://www.iss.it/en/covid-19-primo-piano/-/asset_publisher/yX1afjCDBkWH/content/covid-19-farmaco-anti-hiv-potrebbe-essere-efficace-contro-l-infezione-da-sars-cov-2

Alexpandi 2020 https://pubmed.ncbi.nlm.nih.gov/32793181/

• TDI-015051 – Tuschi Lab’s small molecule inhibitor of the viral guanine-N7 methyltransferase (MTase) NSP14 ✓

NIH Form

Name of intervention: TDI-015051

Type of therapeutic intervention: Drug

Stage of overall development:Preclinical

Symptoms/Syndromes intervention aims to target: Neutralize SARS-CoV-2 by interfering with the viral methyltransferase enzyme NSP14 and preventing SARS-CoV-2 viral replication.

URLs:

Meyer 2024 https://www.nature.com/articles/s41586-024-08320-0

Halford 2024 https://cen.acs.org/pharmaceuticals/drug-discovery/new-way-take-down-SARS/102/web/2024/12

SciTech Daily 2024  https://scitechdaily.com/beyond-paxlovid-scientists-unveil-game-changing-antiviral-that-could-combat-covid-ebola-and-more/

• Truvada (emtricitabine and tenofovir disoproxil fumarate) – Antiretroviral combination therapy used as pre-exposure prophylaxis for HIV and for treatment of Hepatitis B. Also demonstrates effectiveness against EBV reactivation. ✓

NIH Form

Name of intervention: Truvada (emtricitabine and tenofovir disoproxil fumarate)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: SARS-CoV-2 viral persistence

Clinical data for a long COVID-19 indication: Randomized parallel assignment quadruple blinded

Long COVID-19 study status: Ongoing

URLs:

Mt Sinai Clinical Trial 2024 https://clinicaltrials.gov/study/NCT06511063?cond=long%20covid&intr=truvada&rank=1

DeJong 2022

https://pmc.ncbi.nlm.nih.gov/articles/PMC8243808/#:~:text=PWH%20taking%20ART.-,1,supporting%20the%20possibility%20of%20confounding

• VV116 (Deuremidevir) – A Chinese-developed remdesivir derivative and RNA-dependent RNA polymerase inhibitor that has shown efficacy in the treatment of acute COVID and resulted in less viral load and symptom rebound after treatment for acute COVID-19 than nirmatrelvir-ritonavir. First described in November 2020 by a team from Wuhan Institute of Virology and Vigonvita. Available as oral tablets. ✓

NIH Form

Name of intervention: VV116 (Deuremidevir)

Type of therapeutic intervention: Drug

Stage of overall development: Phase 2/3

Symptoms/Syndromes intervention aims to target: SARS-CoV-2 viral persistence

Clinical data for an acute COVID-19 indication: multicenter double-blind randomized controlled study

Acute COVID-19 study status: Completed

URLs:

Fan 2024 https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(23)00577-7/fulltext

Yang 2024 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2816033#google_vignette

• WEHI-P8 – coronaviral protease PLpro inhibitor in the WEHI-P series. ✓

NIH Form

Name of intervention: WEHI-P8

Type of therapeutic intervention: Drug

Stage of overall development: Preclinical

Symptoms/Syndromes intervention aims to target:  reduce the levels of pro-inflammatory cytokines in the lungs; reduce neuroinflammation in the brain

URLs:

Komander 2024 https://www.researchsquare.com/article/rs-4899442/v1

Biologics (monoclonal antibodies, polyclonal antibodies, immune globulins, etc.)

• 5B8 – (MA5-33374) -Invitrogen’s OSCAR anti-fibrin Monoclonal Antibody ✓

NIH Form

Name of intervention: 5B8 (MA5-33374)

Type of therapeutic intervention: Drug

Stage of overall development: Preclinical

Symptoms/Syndromes intervention aims to target: binding the CD11b receptor involved in immune activation to inhibit the fibrin-spike interaction, mitigating clot formation and inflammation

URLs:

Malesu 2024 https://www.news-medical.net/news/20240829/Fibrin-fuels-thromboinflammation-and-brain-damage-in-COVID-19.aspx

Ryu 2024 https://www.nature.com/articles/s41586-024-07873-4

• AER002 – (P2G3) – fully human monoclonal antibody and anti-endothelin receptor B antibody  ✓

NIH Form

Name of intervention: AER002 – (P2G3)

Type of therapeutic intervention: Drug

Stage of overall development: Phase 2

Symptoms/Syndromes intervention aims to target: reducing SARS-CoV-2 viral persistence in patients with Long Covid

Clinical data for Long COVID-19 indication: Double-blind RCT

Long COVID-19 study status: Ongoing

URLs:

Peluso Clinical Trial 2023 Phase 2 https://clinicaltrials.gov/study/NCT05877508

Moullan 2024 https://pmc.ncbi.nlm.nih.gov/articles/PMC10828317

• Bamlanivimab and Etesevimab (LY-CoV016/JS016) – combination of two human recombinant neutralizing IgG1-kappa monoclonal antibodies  ✓

NIH Form

Name of intervention: Bamlanivimab and Etesevimab (LY-CoV016/JS016)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: reducing SARS-CoV-2 viral load and improving clinical outcomes

Clinical data for an acute COVID-19 indication:  RCT

Acute COVID-19 study status: Completed

URLs:

Pitt trial 2022 https://clinicaltrials.gov/study/NCT04790786

Italian trial 2022 https://clinicaltrials.gov/study/NCT05268601

Canada Trial 2022 https://clinicaltrials.gov/study/NCT04748588

Gunaratne 2021 https://pmc.ncbi.nlm.nih.gov/articles/PMC8384088/

Prior EUA 2021-2023 https://www.fda.gov/media/145802/download

• Casirivimab & Imdevimab (Regeneron/REGEN-COV/Ronapreve/REGN10933 and REGN10987) – combination of two recombinant human IgG1 monoclonal antibodies ✓

NIH Form

Name of intervention: Casirivimab & Imdevimab (Regeneron/REGEN-COV/Ronapreve/REGN10933 and REGN10987)

Stage of overall development: Approved for another indication

Type of therapeutic intervention: Drug

Symptoms/Syndromes intervention aims to target: decreasing overall infection rates and reducing SARS-CoV-2 viral load

Clinical data for an acute COVID-19 indication: RCT

Acute COVID-19 study status: Completed

URLs:

USA trial https://clinicaltrials.gov/study/NCT04992273

Canada trial https://clinicaltrials.gov/study/NCT04748588

Italy trial https://clinicaltrials.gov/study/NCT05268601

Dutch trial https://clinicaltrials.gov/study/NCT05195060

Gunaratne 2021 https://pmc.ncbi.nlm.nih.gov/articles/PMC8384088/

• Ofatumumab (Kesimpta/Arzerra) – anti-CD20 monoclonal antibody ✓

NIH Form

Name of intervention: Ofatumumab (Kesimpta/Arzerra)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: improving immune response to SARS-CoV-2

Clinical data for an acute COVID-19 indication: RCT

Acute COVID-19 study status: Completed

URLs:

Novartis Clinical Trial 2024 stage 4 https://clinicaltrials.gov/study/NCT04869358

Wang 2024 https://onlinelibrary.wiley.com/doi/10.1002/acn3.52284

Cross 2022 https://pmc.ncbi.nlm.nih.gov/articles/PMC8918079/

• Pemivibart (Pemgarda/VYD222) – human monoclonal antibody with neutralizing activity against major SARS-CoV-2 variants. ✓

NIH Form

Name of intervention: Pemivibart (Pemgarda/VYD222)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: neutralizing  major SARS-CoV-2 variants, including JN.1.

Clinical data for an acute COVID-19 indication: RCT

Acute COVID-19 study status: Completed

URLs:

Invyvid Phase II Clinical Trial 2024 https://clinicaltrials.gov/study/NCT06039449

FDA EUA Aug 2024 https://www.fda.gov/drugs/emergency-preparedness-drugs/emergency-use-authorizations-drugs-and-non-vaccine-biological-products

• Regdanvimab (Regkirona/CT-P59) – human monoclonal antibody with neutralizing activity against SARS-CoV-2   ✓

NIH Form

Name of intervention: Regdanvimab (Regkirona/CT-P59)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: neutralizing SARS-CoV-2 and reducing viral load

Clinical data for an acute COVID-19 indication:  RCT

Acute COVID-19 study status: Completed

URLs:

Celltron Phase 2/3 Clinical Trial https://clinicaltrials.gov/study/NCT04602000  French Clinical Trial 2022 https://clinicaltrials.gov/study/NCT05439044

EU Authorization 2021 https://www.ema.europa.eu/en/medicines/human/EPAR/regkirona

Jang 2023 https://pmc.ncbi.nlm.nih.gov/articles/PMC9822548/

• SA55 (BD55-5514) – fully humanized monoclonal antibody with neutralizing activity against SARS-CoV-1 & SARS-CoV-2 ✓

NIH Form

Name of intervention: SA55 (BD55-5514)

Type of therapeutic intervention: Drug

Stage of overall development: Phase 2

Symptoms/Syndromes intervention aims to target: neutralizing SARS-CoV-2 and reducing viral load

Clinical data for an acute COVID-19 indication: RCT

Acute COVID-19 study status: Ongoing

URLs:

Sinovac Phase I Clinical Trial 2023 https://clinicaltrials.gov/study/NCT06048393

Sinovac Phase II Clinical Trial 2024 https://clinicaltrials.gov/study/NCT06042764

Cao 2022 https://www.sciencedirect.com/science/article/pii/S2211124722017375

• Sipavibart (Kavigale/AZD3152/Evusheld 2/Supernova)  – RQ Bio and AstraZeneca’s monoclonal antibody with neutralizing activity against SARS-CoV-2.  ✓

NIH Form

Name of intervention: Sipavibart (Kavigale/AZD3152/Evusheld 2)

Type of therapeutic intervention: Drug

Stage of overall development: Phase 2/3

Symptoms/Syndromes intervention aims to target: neutralizing SARS-CoV-2 virus

Clinical data for an acute COVID-19 indication:  RCT

Acute COVID-19 study status: Completed

URLs:

AstraZeneca Clinical Trial Phase 2/3  https://clinicaltrials.gov/study/NCT05648110

AstraZeneca Clinical Trial 2023 https://clinicaltrials.gov/study/NCT05872958   AstraZeneca Clinical Trial Phase I https://clinicaltrials.gov/study/NCT0593264  AstraZeneca Phase 3 https://www.astrazeneca.com/media-centre/press-releases/2024/supernova-trial-met-covid-19-prevention-endpoint.html

EU Authorization https://www.ema.europa.eu/en/documents/smop-initial/chmp-summary-positive-opinion-kavigale_en.pdf

• Sotrovimab – Xevudy (VIR-7831/GSK4182136)   -Vir’s human monoclonal antibody with neutralizing activity against SARS-CoV-2 ✓

NIH Form

Name of intervention: Sotrovimab – Xevudy (VIR-7831/GSK4182136)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: neutralizing SARS-CoV-2 Clinical data for an acute COVID-19 indication: RCT

Acute COVID-19 study status: Completed

URLs:

VIR Phase 3 clinical trial 2023 https://clinicaltrials.gov/study/NCT04913675

US Phase 2 Trial 2023 https://clinicaltrials.gov/study/NCT05210101

US Trial at U.Wash Phase 1 2022 https://clinicaltrials.gov/study/NCT05135650  Prior EUA 2022 https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-sotrovimab-emergency-use-authorization

• Tixagevimab/Cilgavimab  – AstraZeneca’s Evusheld (AZD7442, combining AZD8895/AZD1061) – a combination of two human monoclonal antibodies with neutralizing activity against SARS-CoV-2  ✓

NIH Form

Name of intervention: Tixagevimab/Cilgavimab – Evusheld (AZD7442, combines AZD8895/AZD1061)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: neutralizing SARS-CoV-2 Clinical data for an acute COVID-19 indication: RCT

Acute COVID-19 study status: Completed

URLs:

AstraZeneca Phase 4 Clinical Trial 2023 https://clinicaltrials.gov/study/NCT05569408

Lancet 2022 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00215-6/fulltext

Science Translational Medicine 2022 https://www.science.org/doi/10.1126/scitranslmed.abl8124

• Vilobelimab – (IFX-1/Gohibic)  – InflaRx N.V.’s  chimeric IgG4 anti-C5a monoclonal antibody which blocks C5a as a key “amplifier” of the inflammatory response driving tissue and organ damage.   ✓

NIH Form

Name of intervention: Vilobelimab – (IFX-1/Gohibic)

Type of therapeutic intervention: Drug

Stage of overall development:  Approved for another indication

Symptoms/Syndromes intervention aims to target: control the inflammatory response driving tissue and organ damage by blocking C5a as a key “amplifier” of this response.

Clinical data for an acute COVID-19 indication: RCT

Acute COVID-19 study status: Completed

URLs:

Clinical Trial 2023 https://clinicaltrials.gov/study/NCT04333420

Vlaar 2022 https://pmc.ncbi.nlm.nih.gov/articles/PMC9451499/

EUA 2023 https://www.fda.gov/drugs/drug-safety-and-availability/fda-authorizes-gohibic-vilobelimab-injection-treatment-covid-19

• VIR-7229 – Vir Biotechnology’s human IgG1-kappa SARS-CoV-2 receptor binding domain-targeting monoclonal antibody  ✓

NIH Form

Name of intervention: VIR-7229

Type of therapeutic intervention: Drug

Stage of overall development: Preclinical

Symptoms/Syndromes intervention aims to target: neutralizing SARS-CoV-2 and reducing viral load

URLs:

Rosen 2024 https://pmc.ncbi.nlm.nih.gov/articles/PMC11645210/

Further Notes about Biologicals: 

COVID-19 convalescent plasma: “The advantages are that CCP can be collected soon after individuals in the community are initially infected and identified. In contrast, hyperimmune globulin and mAbs take months or even years to purify, develop, and manufacture. In addition, CCP is polyclonal, so as the virus evolves and individuals develop a new antibody response, CCP continues to provide protection. Hyperimmune globulin is also polyclonal because it is manufactured from a pool of CCP. However, both the time and location of CCP collection compared with administration may influence efficacy because of variant changes.”

• It is with this understanding that CCP could be a critical treatment option for the initial development of Long Covid during a new wave, but tabled when mAbs, hyperimmune globulin, and pAbs have been established since each of these would provide a higher level of neutralizing antibodies.

• Hyperimmune globulin – should be prioritized but only used with a resistance panel and transcriptomic RNA viral load test for the safety of the patient and to accurately measure efficacy.
• pAbs (polyclonal antibodies) – should be prioritized but only used with a resistance panel and transcriptomic RNA viral load test for the safety of the patient and to accurately measure efficacy.
  • pAbs could prove to be more effective than mAbs because they offer a wider range of neutralizing antibodies and potentially less risk for SARS-CoV-2 viral resistance.
  • It’s important to point out that pAbs should not be removed as Long Covid options because of market factors — such as the limited ability to establish patent rights by drug manufacturers. If pAbs can be more effective at eliminating viral load then this must become a priority for research within RECOVER (NIH).
• mAbs (monoclonal antibodies) – should be prioritized but only used with a resistance panel and transcriptomic RNA viral load test for the safety of the patient and to accurately measure efficacy. The following are a list of mAbs that need to be studied for Long Covid:

Other Drugs of Interest

• Anakinra – (Kineret by Swedish Orphan Biovitrum) – immunosuppressant interleukin-1 receptor antagonist protein that blocks immune processes leading to inflammation following SARS-CoV-2 infection. ✓

NIH Form

Name of intervention: Anakinra – (Kineret)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: Reduction of inflammation in SARS-CoV-2

Clinical data for an acute COVID-19 indication:Quadruple-blind RCT

Acute COVID-19 study status: Ongoing

URLs:

Phase 2 Clinical Trial 2023 https://clinicaltrials.gov/study/NCT05926505

Phase 2/3 Clinical Trial 2023 https://clinicaltrials.gov/study/NCT04443881  Phase 3 Clinical Trial U. Oxford https://clinicaltrials.gov/study/NCT0438

UVa study https://www.news-medical.net/news/20240906/Arthritis-medications-could-reverse-COVID-lung-damage.aspx#

• Baricitinib – (Eli Lilly and Incyte’s Olumiant) – Janus kinase (JAK) inhibitor. ✓

NIH Form

Name of intervention: Baricitinib – (Eli Lilly and Incyte’s Olumiant)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: Reduction of systemic and neuroinflammation

Clinical data for an acute COVID-19 indication: Open Label RCT & Double-Blind RCT

Acute COVID-19 study status: Completed

URLs:

REMAP-CAP Phase 3 Clinical Trial 2024 https://clinicaltrials.gov/study/NCT02735707

ACTT NIAID Phase 3 Clinical Trial 2022 https://clinicaltrials.gov/study/NCT04401579

ACTT-4 Phase 3 Clinical Trial 2022 https://clinicaltrials.gov/study/NCT04640168

(Vanderbilt Clinical Trial 2024 https://reporter.nih.gov/search/0ILh2B2lSUybBDyu43zYtQ/project-details/10827260)

• B11-E8-F3 – trivale engineered nanobody with three nanobodies joined tandemly in trivalent form (SN-F3, ZF-B11 and ZF-E8) with antiviral activity against SARS-CoV-1 and SARS-CoV-2. ✓

NIH Form

Name of intervention: B11-E8-F3 engineered nanobody

Type of therapeutic intervention: Drug

Stage of overall development: Preclinical

Symptoms/Syndromes intervention aims to target: neutralize SARS-CoV-2 and reduce SARS-CoV-2 viral load

URLs:

Wang 2024 https://onlinelibrary.wiley.com/doi/10.1002/advs.202402975

• B13-B13-B13 –  multivalent trimeric homotrimer engineered nanobody with neutralization activity against SARS-CoV-2. ✓

NIH Form

Name of intervention: B13-B13-B13 engineered nanobody

Type of therapeutic intervention: Drug

Stage of overall development: Preclinical

Symptoms/Syndromes intervention aims to target: neutralizing SARS-CoV-2

URLs:

Wang 2024 https://onlinelibrary.wiley.com/doi/10.1002/advs.202402975

• BC 007 – German drug that neutralizes functional autoantibodies against G-protein coupled receptors, which disrupt normal cellular functions by binding to cell receptors or other proteins, often imitating or blocking natural signals and resulting in a variety of autoimmune diseases. Administered by infusion. Developed for treatment of heart failure, with publication documenting safety & efficacy. ✓

NIH Form

Name of intervention: BC007

Type of therapeutic intervention: Drug

Stage of overall development: Phase 2/3

Symptoms/syndromes aims to target:  neutralize functional autoantibodies against G-protein coupled receptors, which disrupt normal cellular functions by binding to cell receptors or other proteins

Clinical data for a Long COVID-19 indication: Double-blind RCT

Long COVID-19 study status: Completed, analysis available

URLs:

Clinical Trials 2024 https://clinicaltrials.gov/study/NCT05911009?cond=long%20covid&intr=BC%20007&rank=1

Hohberger 2024 https://www.medrxiv.org/content/10.1101/2024.12.13.24318856v1.full.pdf

• Cycloferon (CMA, 10-carboxymethyl-9-acridanone) – Russian low molecular weight drug that induces interferon production, providing antiviral and immunomodulatory effects. Currently used in treatment of herpes and respiratory viral infections. Also has demonstrated direct (non-IFN-mediated) antiviral activity against adenovirus in vitro. ✓

NIH Form

Name of intervention: Cycloferon (CMA, 10-carboxymethyl-9-acridanone)

Type of therapeutic intervention: Drug

Stage of overall development:  Approved for another indication

Symptoms/Syndromes intervention aims to target: Reduction in SARS-CoV-2 viral persistence; immunomodulation

URLs:

Mazin 2022 https://www.antibiotics-chemotherapy.ru/jour/article/view/929

Mazina 2017 https://www.researchgate.net/publication/321955489_Clinical_efficacy_of_the_immunomodulatory_agent_cycloferon_tablets_in_viral_respiratory_infections_Results_of_a_systematic_review_and_meta-analysis

Zarubaev 2003 https://www.sciencedirect.com/science/article/abs/pii/S0166354202001936

• Cefuroxime (Zinacef/Ceftin) – cephalosporin small molecule antibiotic with antiviral action that inhibits 3 main proteins  (protease, RNA dependent polymerase and ACE2 spike complex) ✓

NIH Form

Name of intervention: Cefuroxime – (Zinacef/Ceftin)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: antiviral action against SARS-CoV-2 viral persistence

URLs:

Durojaiye 2020 https://pmc.ncbi.nlm.nih.gov/articles/PMC7298880/

ASC Focus 2020 https://www.ascfocus.org/ascfocus/content/articles-content/articles/2020/digital-debut/fda-updates-extended-use-drugs-list-to-meet-covid-19-demands

Hu 2021 https://pmc.ncbi.nlm.nih.gov/articles/PMC7919521/

Yacouba 2021 https://pmc.ncbi.nlm.nih.gov/articles/PMC8139224/

Sharma 2022 https://www.jetir.org/view?paper=JETIR2201310

• diABZI-4 (Diamidobenzimidazole/CAS# 2138299-34-8) –  InvivoGen’s STING interferon agonist (synthetic compound) ✓

NIH Form

Name of intervention: diABZI-4 (Diamidobenzimidazole/CAS# 2138299-34-8)

Type of therapeutic intervention: Drug

Stage of overall development: Preclinical

Symptoms/Syndromes intervention aims to target: reduce inflammation; inhibit coronavirus infection by disrupting the formation of viral replication organelles

URLs:

Invivogen1 https://www.invivogen.com/diabzi-sting-agonist

Song 2024 https://onlinelibrary.wiley.com/doi/10.1002/jmv.70020

• Eukarion 8 (EUK8) – A mitochondria-targeted antioxidant that inhibits mROS (mitochondrial reactive oxygen species), thereby reducing HIF-1alpha, viral proteins, and inflammatory cytokines. Process would not be susceptible to SARS2 mutation resistance. Thus far, only tested in mice. ✓

NIH Form

Name of intervention: Eukarion 8 (EUK8)

Type of therapeutic intervention: Drug

Stage of overall development: Preclinical

Symptoms/Syndromes intervention aims to target: Reduction of SARS-CoV-2 viral load and inflammation, modulation of immune system

Clinical data for an acute COVID-19 indication: murine study

URLs:

Guarnieri 2024 https://pubmed.ncbi.nlm.nih.gov/39008677/

• Galectin 1 and Galectin 3 inhibitors (Prolectin M, Prolectin L, Galectovid, others) – guar gum-derived carbohydrates that reduce SARS-CoV-2 viral load by competitively inhibiting viral binding to cell surface glycans. ✓

NIH Form

Name of intervention: Galectin 1 and Galectin 3 inhibitors (Prolectin M, Galectovid, others)

Type of therapeutic intervention: Drug

Stage of overall development: Phase 2/3

Symptoms/Syndromes intervention aims to target: Reduction of SARS-CoV-2 viral load and inflammation

Clinical data for an acute COVID-19 indication: randomised double-blind   placebo-controlled clinical trial

Acute COVID-19 study status: Completed

URLs:

Miller 2024 https://esmed.org/MRA/mra/article/view/5616

Ahmed 2023 https://pmc.ncbi.nlm.nih.gov/articles/PMC10179732/#sec2-ijms-24-08116

Sigamani 2023 https://pmc.ncbi.nlm.nih.gov/articles/PMC10140888/

Sigamani 2022a https://assets-eu.researchsquare.com/files/rs-1531940/v1/a5d50c07-9097-4f89-8d5f-cece8a907b56.pdf?c=1659741254

Sigamani 2022b

https://www.researchgate.net/publication/362361449_Carbohydrate_prolectin-M_a_galectin-3_antagonist_blocks_SARS-CoV-2_activity

(Sigamani 2020 https://www.medrxiv.org/content/10.1101/2020.12.03.20238840v2

Sakai 2022 https://pubmed.ncbi.nlm.nih.gov/35916813/

• Interferon lambda (pegylated interferon lambda) – reducing viral load and hyperinflammation  ✓

NIH Form

Name of intervention: Interferon lambda (pegylated interferon lambda)

Type of therapeutic intervention: Drug

Stage of overall development: Phase 2/3

Symptoms/Syndromes intervention aims to target: Reduction of viral load and hyperinflammation`

Clinical data for an acute COVID-19 indication: Double-blind RCT

Acute COVID-19 study status: Completed, analysis available

URLs:

NEJM 2023 https://www.nejm.org/doi/full/10.1056/NEJMc2303519

McCarthy 2023 https://pubmed.ncbi.nlm.nih.gov/37147857/

Stanford Clinical Trial 2021 https://clinicaltrials.gov/study/NCT04331899

• NACE2i – peptide inhibitor of ACE2 that inhibits viral replication, prevents inflammation and macrophage infiltration. ✓

NIH Form

Name of intervention: NACE2i

Type of therapeutic intervention: Drug

Stage of overall development: Preclinical

Symptoms/Syndromes intervention aims to target: inhibiting viral replication, preventing inflammation and macrophage infiltration

URLs:

Tu 2023 https://www.nature.com/articles/s41467-023-39341-4

Medical Xpress 2023 https://medicalxpress.com/news/2023-06-drug-covid-re-infection.html

• Nitazoxanide – (Alinia) antiprotozoal drug – antiparasitic and antiviral. ✓

NIH Form

Name of intervention: Nitazoxanide – (Alinia)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: reduce SARS-CoV-2 viral load

Clinical data for an acute COVID-19 indication:double-blind RCT

Acute COVID-19 study status: Completed

URLs:

US Phase 3 Clinical Trial 2021 https://clinicaltrials.gov/study/NCT04359680  Stewart 2023 https://pmc.ncbi.nlm.nih.gov/articles/PMC10654558/

Rocco 2021 https://publications.ersnet.org/content/erj/58/1/2003725

South Africa Clinical Trial 2024 https://clinicaltrials.gov/study/NCT04746183  Brazil Clinical Trial 2020 https://clinicaltrials.gov/study/NCT04561219

Egypt Clinical Trial 2020 https://clinicaltrials.gov/study/NCT04498936

• Rapamycin (Sirolimus/Rapamune)  – antibiotic, immunosuppressant, and serine/threonine kinase inhibitor; affects PI3K/AKT/mTOR pathway which inhibited MERS-CoV activity; inhibition of mTOR increases lifespan;  inhibits muscle protein synthesis/muscle wasting   ✓

NIH Form

Name of intervention: Rapamycin (Sirolimus/Rapamune)

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: reducing viral persistence, improving immune function & inhibiting muscle wasting

Clinical data for an acute COVID-19 indication:double blind RCT

Acute COVID-19 study status: Completed

URLs:

PolyBio study https://polybio.org/projects/long-covid-low-dose-rapamycin-clinical-trial/

Texas  Phase 2 double blind RCT https://clinicaltrials.gov/study/NCT04482712

Chicago 2021 https://clinicaltrials.gov/study/NCT04948203

Simmaron 2023 Clinical Trial https://clinicaltrials.gov/study/NCT06257420   Egypt Clinical Trial 2020 https://clinicaltrials.gov/study/NCT04461340

Lees 2022 https://pmc.ncbi.nlm.nih.gov/articles/PMC9169843/

Bischof et al. 2021 https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(20)30068-4/fulltext

• Pantethine – B5 vitamin derivative hypolipidemic agent, dimer of pantetheine, an amide analogue of pantothenic acid.  ✓

NIH Form

Name of intervention: Pantethine

Type of therapeutic intervention: Drug

Stage of overall development: Preclinical

Symptoms/Syndromes intervention aims to target: lower lipid and inhibit cholesterol synthesis, interfering with SARS-CoV-2  interaction with cellular cholesterol

URLs:

Abou-Hamdan 2023 https://pmc.ncbi.nlm.nih.gov/articles/PMC9906591/  Grewal 2024 https://www.life-science-alliance.org/content/7/5/e202302453

• Sulfoglycodendron antivirals –  sulfoglycodendron broad-spectrum antivirals block multiprotein human heparan sulfate proteoglycans receptors in SARS-CoV-2 ✓

NIH Form

Name of intervention: Sulfoglycodendron antivirals

Type of therapeutic intervention:  Drug

Stage of overall development: Preclinical

Symptoms/Syndromes intervention aims to target: neutralizing SARS-CoV-2

URLs:

Coppola 2024  https://pubs.acs.org/doi/10.1021/acs.jcim.4c00541

• Sulodexide – Used prophylactically and in treatment of thromboembolic diseases. Beneficial in reperfusion injury, the treatment of diabetic nephropathy, tinnitus, and chronic venous disease. Demonstrated to reduce endothelial dysfunction in acute Covid. Approved in numerous countries in Europe, South America, and Asia, but not in US. ✓

NIH Form

Name of intervention: Sulodexide

Type of therapeutic intervention: Drug

Stage of overall development: Approved for another indication

Symptoms/Syndromes intervention aims to target: Long Covid endothelial dysfunction

Clinical data for an acute COVID-19 indication: Randomized controlled trial

Acute COVID-19 study status: Completed

URLs:

Gonzalez-Ochoa 2021 https://pmc.ncbi.nlm.nih.gov/articles/PMC7882918/

Fareed 2024 https://ashpublications.org/blood/article/144/Supplement%201/5521/527358/Oral-Sulodexide-Downregulates-Biomarkers-of

Rajewska-Tabor 2023 https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1268016/full

• Tri-TMV (Ty1,  MR17-K99Y & VHH V)  –  engineered nanobody consisting of Ty1,  MR17-K99Y and VHH V with neutralization activity against SARS-CoV-2. ✓

NIH Form

Name of intervention: Tri-TMV (Ty1,  MR17-K99Y & VHH V) engineered nanobody

Type of therapeutic intervention: Drug

Stage of overall development: Preclinical

Symptoms/Syndromes intervention aims to target: neutralizing SARS-CoV-2

URLs:

Hannula 2024 https://pmc.ncbi.nlm.nih.gov/articles/PMC10986514/

• TVGN 489 – Tevogen Bio’s allogeneic Cytotoxic CD8+ T lymphocytes (CTLs) immunotherapy

NIH Form

Name of intervention: TVGN 489

Type of therapeutic intervention: Drug

Stage of overall development: Phase I

Symptoms/Syndromes intervention aims to target: reduce viral load; detect and kill SARS-CoV-2 infected cells

Clinical data for an acute COVID-19 indication: Open Label RCT

Acute COVID-19 study status: Ongoing

URLs:

Synapse 2024 https://synapse.patsnap.com/article/tevogen-bio-confirms-efficacy-of-tvgn-489-against-flirt-strains-of-sars-cov-2

Tevogen 2024 https://tevogen.com/press_release/tevogen-bio-confirms-ongoing-efficacy-of-tvgn-489-its-investigational-allogeneic-off-the-shelf-immunotherapy-against-dominant-flirt-strains-of-sars-cov-2/

Yahoo 2024 https://finance.yahoo.com/news/tevogen-bio-announces-publication-positive-120500268.html

BioPharm 2021  https://www.biopharminternational.com/view/fda-clears-tevogen-bios-ind-application-for-ctl-covid-19-treatment

Clinical Trials Arena 2022 https://www.clinicaltrialsarena.com/news/tevogen-cell-therapy-covid/

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