| Ribavirin (FDA, EMA) |
Guanosine analog: multiple proposed MOAs (IMPDH inhibition, lethal mutagenesis) |
15 families (very broad): e.g. Arenaviridae (Lassa, Junin), Flaviviridae (HCV, dengue, WNV, Zika), Paramyxoviridae (RSV, measles), Orthomyxoviridae (influenza), Filoviridae (Ebola), Coronaviridae (SARS, MERS), etc. |
15 |
Approved (since 1985) |
RSV (aerosol in immunocompromised); HCV (in combination therapy); viral hemorrhagic fevers (off-label). |
IC₅₀: In vitro nanomolar to micromolar for many viruses; e.g. Lassa virus EC₅₀ ≈ micromolar. Protects NHPs from filovirus and arenavirus challenge. In HCV, combos (with IFN) yield SVR ~50–75%. Reduces Lassa mortality (historical control); mixed results in Ebola/COVID (no benefit in trials). |
Hemolytic anemia, teratogenic; aerosol formulation limited use. Oral/inhaled dosing varies (e.g. RSV inhalation; HCV: 600–1200 mg daily). Teratogenicity is major limitation. |
Poor monotherapy efficacy; resistance can arise (RdRp fidelity mutants). Broad activity often only at high doses (toxicity). |
235; ClinicalTrials.gov for RSV/HCV. |
| Interferon-α (pegylated) (FDA, EMA) |
Host immune modulator: stimulates Type-I IFN response, inducing antiviral state (STAT1/2 pathway). |
≥ many families: Shown to inhibit numerous viruses (HCV, HBV, HPV, certain corona, etc) in vitro/clinic. Approved for chronic HCV and HBV; also in rare viral oncotherapy. |
(host-target) |
Approved (IFN-α2b/2a for HCV, HBV) |
Efficacy driven by immune activation: e.g. >50% SVR in HCV when combined with ribavirin. Also effective vs HPV (warts), HDV (unique efficacy). |
Flu-like side effects, depression, cytopenias; injectable weekly dosing (180 µg pegIFN-α2a weekly). |
Systemic toxicity limits use; variable response; no virus-specific resistance but some viruses evolve IFN evasion. |
Guidelines (FDA labels), [52] (IFN antiviral mechanisms). |
| Remdesivir (Veklury) (FDA, EMA) |
Adenosine nucleotide analog: delayed chain terminator of viral RdRp. |
RNA viruses (especially Filoviridae and Coronaviridae): active vs EBOV in NHPs (100% survival); broad in vitro vs SARS-CoV-1/2, MERS, Nipah virus (Paramyxoviridae) in models. Also suppresses RSV and paramyxoviruses in vitro/NHP. |
~4 (Filoviridae, Coronaviridae, Paramyxoviridae, possibly others) |
Approved (2020) |
In vitro: EBOV IC₅₀ ~100 nM; SARS-CoV-2 in cell culture IC₅₀ ~770 nM. Animal: protects NHPs from EBOV and MERS. Clinical: in ACTT-1 trial (N=1062) reduced COVID-19 recovery time (median 10→7 days) and mortality. |
IV infusion (200 mg loading, then 100 mg daily). Generally well tolerated; some hepatotoxicity, infusion reactions. |
IV-only (limit ambulatory use). Resistance mutations in RdRp observed in vitro; limited efficacy in later COVID variants. |
11917; FDA label. |
| Molnupiravir (Lagevrio) (FDA EUA/EMA) |
Oral ribonucleoside analog: causes lethal mutagenesis via viral RdRp (NHC). |
Broad RNA viruses: active vs SARS-CoV-2 (approved for COVID), influenza A/B, alphaviruses, filoviruses, coronaviruses (SARS/MERS) in animal models. (Designed for VEEV.) |
6 (CoV, Orthomyxo, Togavirus, Flavivirus, Hepacivirus?, arenavirus?…) |
Approved EUA (2021) |
In vitro: SARS-CoV-2 EC₅₀ ~0.67–2.7 µM; active vs influenza and Ebola in animals. Clinical: Phase III COVID-19 (MOVe-OUT) halved hospitalization/death risk (7.3% vs 14.1%). Antiviral effect: reduced viral load in early trials. |
800 mg PO BID ×5 days. Side effects mild (headache, diarrhea). No teratogenicity seen in human trials, but contraindicated in pregnancy due to mutagenicity risk. |
Lower efficacy than expected (smaller risk reduction on full analysis); potential mutagenesis concern (long-term risks under study). |
181920; NCT NCT04575597 (EUA data). |
| Favipiravir (Avigan) (Japan, CN, RU) |
Oral purine nucleoside analog: inhibits viral RdRp (lethal mutagenesis). |
Negative-sense RNA viruses: approved for influenza (Orthomyxo); in vitro/in vivo vs influenza A/B, arenaviruses, flaviviruses (e.g. SFTSV), SARS-CoV-2 (Coronaviridae). Also tested in Ebola (Filoviridae) in vitro. |
5 (Orthomyxo, Arenaviridae, Flaviviridae, Coronaviridae, Phenuivirus etc) |
Approved (2014 JP; 2020 China, Russia COVID use) |
In vitro: moderate influenza (EC₅₀ ~10–60 µM), weak SARS-CoV-2 (EC₅₀ ~61 µM). Animal: protected mice from lethal SFTSV (Phlebovirus). Clinical: influenza trial (Japan) showed faster viral clearance; mixed COVID results (small benefit in early studies). |
1600 mg PO BID Day1, then 600–800 mg BID ×4 days (influenza dosing). Generally well tolerated; teratogenic (contraindicated in pregnancy). |
High EC₅₀, limited monotherapy efficacy (COVID RCTs negative); requires high dose. Pregnancy ban limits use. |
2630; NCT NCT04405441 etc. |
| Umifenovir (Arbidol) (China, Russia) |
Membrane fusion inhibitor: intercalates into lipid envelope/viral glycoprotein (e.g. influenza HA), preventing fusion. Also immunomodulatory (induces IFN). |
RNA viruses: approved for influenza A/B (Orthomyxoviridae); active in vitro against flaviviruses (Zika, WNV, TBEV; Flaviviridae), coronaviruses (SARS-CoV-2), paramyxovirus (RSV), and others. |
3 (Orthomyxo, Flavi, Paramyxo) |
Approved (RU, CN) |
In vitro: ZIKV/WNV/TBEV EC₅₀ ~10–19 μM. Influenza trials (Russia/China) showed modest symptom reduction. Limited COVID data (small observational studies). |
200 mg PO TID (influenza dosing). Good safety. |
Limited clinical data outside influenza; not approved by FDA/EMA. Cell-type–dependent activity may limit systemic efficacy. |
32; Observational COVID studies (e.g. ChiCTR2000029573). |
| Brincidofovir (Tembexa) (FDA) |
Oral lipid-conjugated cidofovir: DNA polymerase inhibitor (chain termination). |
Double-stranded DNA viruses: approved for smallpox (Poxviridae); active vs adenovirus, CMV, EBV (Herpesviridae), BKV (Polyomaviridae) in vitro/in vivo. |
3 (Pox, Herpes, Adeno) |
Approved (2021) |
Animal models: protective in orthopoxvirus challenge (basis for approval). Phase II/III trials: reduced adenovirus and CMV viremia in transplant patients. No RCTs in smallpox (ethical constraints). |
200 mg PO once, then 100 mg weekly (2 doses total). Diarrhea, GI intolerance, liver enzyme elevations (boxed warning). |
No observed efficacy in monkeypox/variola treatment in humans; liver toxicity significant. |
3534; NCT NCT02113759. |
| Other approved BSAs |
Peg-IFN-λ (novel IFN for hepatitis; similar host-target broad action), Cidofovir (Vistide) (approved for CMV retinitis; broad anti-DNA virus activity), Nelfinavir/Lopinavir (HIV PIs, weak off-target coronavirus activity, no proven broad-spectrum use), Nitazoxanide (antiprotozoal with broad in vitro antiviral profile; not FDA-approved for viruses), Merimepodib (DHODH inhibitor; only investigational). Each of these has narrower or host-mediated spectra with notable limitations (e.g. toxicity, equivocal efficacy). |
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