List of investigational long COVID drugs
This is a list of investigational long COVID drugs, or drugs that are currently under development for clinical use for the treatment of post-acute COVID-19 syndrome (long COVID) but are not yet approved.
Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. The format of list items is "Name (Synonyms) – Mechanism of Action [Reference]".
This list was last comprehensively updated in September 2025. It is likely to become outdated with time.
Under development
Phase 2/3
- Ibudilast (AV-411; Eyevinal; Ibinal; KC-404; Ketas; MN-166; Pinatos) – phosphodiesterase PDE4 inhibitor and toll-like receptor 4 (TLR4) antagonist [1]
- Sodium pyruvate (EmphyClear; N115) – various actions [2]
Phase 2
- AER-002 – monoclonal antibody against SARS-CoV-2 spike protein [3]
- Allogeneic human umbilical cord blood haematopoietic progenitor cell therapy (Regenecyte; HPC-cord blood) – cell replacement [4]
- Bezisterim (HE-3286; NE-3107; Triolex; 17α-ethynyl-5-androstene-3β,7β,17β-triol) – undefined mechanism of action (synthetic androstenetriol analogue and anti-inflammatory) [5]
- Celecoxib/valacyclovir (IMC-2) – combination of celecoxib (COX-2 inhibitor/NSAID) and valacyclovir (antiviral/viral DNA polymerase inhibitor) [6]
- Cyclobenzaprine (KRL-102; TNX-102; Tonmya) – tricyclic antidepressant (monoamine reuptake inhibitor and monoamine receptor modulator) [7]
- Leronlimab (PA-14; PRO-140; Vyrologix) – monoclonal antibody against CCR5 [8]
- Nogapendekin alfa inbakicept (ALT-803; Anktiva; IL-15N72D/IL-15Ra-Fc; N-803; VesAnktiva) – fusion protein and interleukin-15 receptor agonist [9]
- Rintatolimod (AMP-516; AMP-518; Ampligen; Atvogen; Rintamod; PolyI:PolyC12U) – mismatched double-stranded polymer of RNA (dsRNA) and toll-like receptor 3 (TLR3) agonist [10]
- Rovunaptabin (BC-007) – oligonucleotide aptamer (binds to and neutralizes autoantibodies against GPCRs) [11]
- RSLV-132 – fusion protein (RNase fused to the Fc domain of IgG1) [12]
- Sipavibart (AZD-3152; Kavigale) – monoclonal antibody against SARS-CoV-2 spike protein [13]
- Temelimab (GENHP-01; GNbAC-1; GNN-001) – monoclonal antibody against human endogenous retrovirus-W (HERV-W) and consequent toll-like receptor 4 (TLR4) inhibitor [14]
- Vidofludimus calcium (4SC-101; IM-90838; IMU-838; SC-12267; VidoCa) – dihydroorotate dehydrogenase (DHODH) inhibitor and Nurr1 activator [15]
Preclinical
- Foralumab (NI-0401; NI-0401/α-CD3; TZLS-401) – monoclonal antibody against CD3 [16]
- LTI-2355 – phagocyte modulator [17]
- Maraviroc/atorvastatin – combination of maraviroc (antiviral/CCR5 receptor antagonist) and atorvastatin (statin) [18]
Research
- SFA-006 – GPR43 modulator [19]
Clinical phase unknown
- Ensitrelvir (S-217622; Xocova) – antiviral (coronavirus 3C-like proteinase inhibitor) [20]
- Lidocaine delivered in complex with HP-β-cyclodextrin; investigated for long COVID following a 36-week prospective observational interrupted time-series study reporting symptom improvement [21]
Not under development
Discontinued
- AXA-1125 (AXA1125) – combination of five amino acids (leucine, isoleucine, valine, arginine, and glutamine) and an amino acid derivative (N-acetylcysteine) ("increases β-oxidation and improves bioenergetics") [22]
- Deupirfenidone (deuterated pirfenidone; LYT-100; LYT-100-COV; LYT-100-ILD; LYT-100-LYMPH; SD-560) – deuterated pirfenidone (collagen inhibitor and anti-inflammatory/immunomodulator) [23]
- DMI-9523 (Ampion; DA-DKP; LMWF-5A) – nuclear factor NF-κB activation inhibitor and anti-inflammatory [24]
Clinically used drugs
Approved drugs
- None
Off-label drugs
- α2-Adrenergic receptor agonists (e.g., clonidine, guanfacine)[1][2][3]
- AMPA receptor antagonists (e.g., perampanel)[4]
- Analgesics (e.g., acetaminophen, NSAIDs)[1]
- Antidepressants (e.g., SSRIs, SNRIs, TCAs, mirtazapine, bupropion, trazodone, vortioxetine, St. John's wort)[5][1]
- Antihistamines (H1 receptor antagonists) (e.g., cetirizine, fexofenadine, loratadine)[5]
- Antivirals (e.g., lopinavir/ritonavir, acyclovir, nirmatrelvir/ritonavir, remdesivir)[5][2][6][7]
- Atypical antipsychotics (e.g., aripiprazole, risperidone, brexpiprazole, quetiapine)[5]
- Beta blockers (e.g., propranolol, metoprolol)[5][1]
- C1 esterase inhibitor (recombinant)[5]
- Corticosteroids (e.g., hydrocortisone, dexamethasone)[5][1][2][8]
- Fluvoxamine (Luvox)[6][9]
- Histamine H2 receptor antagonists (e.g., famotidine)[5]
- Immunoglobulin (intravenous)[5]
- Melatonin[5]
- Monoclonal antibodies (e.g., adalimumab, infliximab)[5][2]
- N-Acetylcysteine (NAC)[10][2]
- Naltrexone (low-dose)[5][2]
- Probiotics and prebiotics[10][2]
- Serotonergic psychedelics (e.g., psilocybin)[11][12]
- Sleep aids (e.g., orexin receptor antagonists, benzodiazepines, Z-drugs, melatonin, herbal sleep aids)[5][13]
- Stimulants (e.g., amphetamine, methylphenidate)[5][14][13]
- Vitamins, minerals, and other dietary supplements (e.g., coenzyme Q10, selenium, B vitamins, vitamin D, iron, omega-3 fatty acids, magnesium, carnitine)[5][2][15]
- Wakefulness-promoting agents (e.g., modafinil, armodafinil)[5][13][16]
See also
- List of investigational drugs
- List of investigational ME/CFS drugs
- List of investigational fibromyalgia drugs
- List of investigational fatigue drugs
References
- ^ a b c d e Seo JW, Kim SE, Kim Y, Kim EJ, Kim T, Kim T, Lee SH, Lee E, Lee J, Seo YB, Jeong YH, Jung YH, Choi YJ, Song JY (March 2024). "Updated Clinical Practice Guidelines for the Diagnosis and Management of Long COVID". Infect Chemother. 56 (1): 122–157. doi:10.3947/ic.2024.0024. PMC 10990882. PMID 38527781.
- ^ a b c d e f g h Munipalli, Bala; Dawson, Nancy L.; Rosales, Juan C. Cardenas; Paul, Stefan N.; Delaney, Troy R.; Morris, Anjali M.; Brigham, Tara J.; Robinson, Arden R.; Dabrh, Abd Moain Abu (14 April 2025). "Pharmacologic and Nonpharmacologic Treatment of Long COVID: A Meta-narrative Review". SN Comprehensive Clinical Medicine. 7 (1) 82. doi:10.1007/s42399-025-01837-z. ISSN 2523-8973. Retrieved 17 September 2025.
- ^ Kondo T, Higa R, Kuniba M, Shinzato H, Takaesu Y (September 2024). "Successful treatment with guanfacine in a long-COVID case manifesting marked cognitive impairment". Neuropsychopharmacol Rep. 44 (3): 585–590. doi:10.1002/npr2.12466. PMC 11544435. PMID 38934345.
- ^ Fujimoto Y, Abe H, Eiro T, Tsugawa S, Tanaka M, Hatano M, Nakajima W, Ichijo S, Arisawa T, Takada Y, Kimura K, Sano A, Hirahata K, Sasaki N, Kimura Y, Takahashi T (2025). "Systemic increase of AMPA receptors associated with cognitive impairment of long COVID". Brain Commun. 7 (5) fcaf337. doi:10.1093/braincomms/fcaf337. PMC 12483584. PMID 41036177.
- ^ a b c d e f g h i j k l m n o p Ivlev I, Wagner J, Phillips T, Treadwell JR (July 2025). "Interventions for Long COVID: A Narrative Review". J Gen Intern Med. 40 (9): 2005–2023. doi:10.1007/s11606-024-09254-z. PMC 12325819. PMID 39984803.
- ^ a b Hashimoto K (2023). "Overview of the potential use of fluvoxamine for COVID-19 and long COVID". Discov Ment Health. 3 (1) 9. doi:10.1007/s44192-023-00036-3. PMC 10029802. PMID 36968793.
- ^ German ER, Jairath MK, Caston J (April 2023). "Treatment of Long-Haul COVID Patients With Off-Label Acyclovir". Cureus. 15 (4) e37926. doi:10.7759/cureus.37926. PMC 10205150. PMID 37228547.
- ^ Yavropoulou MP, Tsokos GC, Chrousos GP, Sfikakis PP (December 2022). "Protracted stress-induced hypocortisolemia may account for the clinical and immune manifestations of Long COVID". Clin Immunol. 245 109133. doi:10.1016/j.clim.2022.109133. PMC 9519365. PMID 36182048.
- ^ Ramonfaur D, Ayad N, Liu PH, Zhou J, Wu Y, Li J, Chen G (September 2024). "The global clinical studies of long COVID". Int J Infect Dis. 146 107105. doi:10.1016/j.ijid.2024.107105. PMID 38782355.
- ^ a b Griffin DO (September 2024). "Postacute Sequelae of COVID (PASC or Long COVID): An Evidenced-Based Approach". Open Forum Infect Dis. 11 (9) ofae462. doi:10.1093/ofid/ofae462. PMC 11363684. PMID 39220656.
- ^ Low ZX, Yong SJ, Alrasheed HA, Al-Subaie MF, Al Kaabi NA, Alfaresi M, Albayat H, Alotaibi J, Al Bshabshe A, Alwashmi AS, Sabour AA, Alshiekheid MA, Almansour ZH, Alharthi H, Al Ali HA, Almoumen AA, Alqasimi NA, AlSaihati H, Rodriguez-Morales AJ, Rabaan AA (March 2025). "Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review". Prog Neuropsychopharmacol Biol Psychiatry. 137 111279. doi:10.1016/j.pnpbp.2025.111279. PMID 39909170.
- ^ Bobak L, Dorney I, Kovacevich A, Barnett BS (March 2025). "Therapeutic Potential of Psilocybin for Treating Neuropsychiatric Long COVID Symptoms: A Reddit Investigation". J Psychoactive Drugs: 1–9. doi:10.1080/02791072.2025.2478097. PMID 40084630.
- ^ a b c Lee, Elliott K; Auger, R. Robert (23 April 2024). "Sleep and Long COVID—A Review and Exploration of Sleep Disturbances in Post Acute Sequelae of SARS-COV-2 (PASC) and Therapeutic Possibilities". Current Sleep Medicine Reports. 10 (2): 169–180. doi:10.1007/s40675-024-00299-4. ISSN 2198-6401. Retrieved 17 September 2025.
- ^ Koonce RM, Martin BC (January 2024). "The association between suspected long-COVID and stimulant prescribing in the United States". Psychiatry Res. 331 115686. doi:10.1016/j.psychres.2023.115686. PMC 10797645. PMID 38142603.
- ^ Vaziri-Harami R, Delkash P (January 2022). "Can l-carnitine reduce post-COVID-19 fatigue?". Ann Med Surg (Lond). 73 103145. doi:10.1016/j.amsu.2021.103145. PMC 8667465. PMID 34925826.
- ^ Pliszka, Andrew G. (28 June 2022). "Modafinil: A Review and Its Potential Use in the Treatment of Long COVID Fatigue and Neurocognitive Deficits". American Journal of Psychiatry Residents' Journal. 17 (4): 5–7. doi:10.1176/appi.ajp-rj.2022.170402. ISSN 2474-4662.