COVID-19 treatment: high-profit systemic drugs

Over 10,000 compounds predicted to reduce risk—SARS-CoV-2 easily disabled SARS-CoV-2 infection involves a complex interplay of over 350 host and viral proteins and other factors1-94, providing many therapeutic targets. Scientists have identified 10,580+ compounds95 potentially beneficial for COVID-19. Hundreds of compounds inhibit SARS-CoV-2 in vitro, including many with known pharmacokinetics and proven safety.

Paxlovid Paxlovid was effective97-181, but has significant side effects, increased risk of replication-competent viral rebound127, and extensive contraindications182,183. Resistant variants are likely184-191 and current efficacy may be lower. The degree of efficacy is unclear—Pfizer RCTs report good results, while independent RCTs119,163 show poor results, consistent with meta-analysis showing that industry-sponsored studies are more likely to be favorable192. Pfizer denied access for other independent trials193. The largest RCT, the 3,371 patient PANORAMIC trial started in April 2022, did not release any results during the pandemic—results were unknown prior to leaking from an embargoed database entry in October 2025194. About one third of people may be at risk of a major/contraindicated drug interaction, which may increase for patients over 60 or with comorbidities that also increase COVID-19 risk183,195. Hoertel et al.196 found that over 50% of COVID-19 patients who died had a contraindication for paxlovid. Use may promote the emergence of variants that weaken host immunity and contribute to long COVID197. Observational studies are often highly confounded—in population studies patients that seek out and receive paxlovid may also be more health-conscious, be more likely to take additional measures or known beneficial non-prescription treatments, and have improved access to the medical system. Malden et al. confirm this, showing that treated patients are more likely to be from affluent neighborhoods, be more health-conscious, and have better access to care. Studies are also often confounded via immortal time bias and failure to exclude contraindicated patients in the control group.

3CLpro inhibitors Paxlovid inhibits SARS-CoV-2 3CLpro, a key enzyme in the viral replication process. In addition to existing compounds that function as 3CLpro inhibitors such as quercetin and curcumin, many novel compounds have been developed. Paxlovid is unlikely to be the most effective, the safest179,196,199,200, or the most resistant to variants184-191, however it is the most profitable. Other novel 3CLpro inhibitors showing lower COVID-19 risk include atilotrelvir, ibuzatrelvir, and leritrelvir201-207.

Molnupiravir Molnupiravir is likely effective139,146,152,153,174,175,209-254, with precise efficacy unclear due to similar issues regarding conflicts of interest in RCTs and confounding in population studies. However, potential mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity241,255-268, the increased risk of creating new dangerous variants269-273, an association with increased viral persistence241, and the existence of many other options rule out use in humans. Molnupiravir has been used for creating variants to test the resistance of treatments to escape mutations274.

Systemic antivirals may be less applicable to low-risk infections As SARS-CoV-2 has evolved, the frequency of serious cases has reduced. Systemic antivirals may have a more limited effect if infection does not spread beyond the upper respiratory tract.

Protocols combine multiple treatments No single treatment is guaranteed to be effective and safe for a specific individual. Leading evidence-based protocols combine multiple treatments.