c19early.org
COVID-19 Treatment Clinical Evidence
COVID-19 involves the interplay of 500+ viral and host proteins and factors, providing many therapeutic targets.
c19early analyzes 6,000+ studies for 220+ treatments—over 17 million hours of research.
Only three high-profit early treatments are approved in the US.
In reality, many treatments reduce risk,
with 26 low-cost treatments approved across 163 countries.
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Naso/
oropharyngeal treatment Effective Treatment directly to the primary source of initial infection. -
Healthy lifestyles Protective Exercise, sunlight, a healthy diet, and good sleep all reduce risk.
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Immune support Effective Vitamins A, C, D, and zinc show reduced risk, as with other viruses.
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Thermotherapy Effective Methods for increasing internal body temperature, enhancing immune system function.
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Systemic agents Effective Many systemic agents reduce risk, and may be required when infection progresses.
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High-profit systemic agents Conditional Effective, but with greater access and cost barriers.
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Monoclonal antibodies Limited Utility Effective but rarely used—high cost, variant dependence, IV/SC admin.
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Acetaminophen Harmful Increased risk of severe outcomes and mortality.
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Remdesivir Harmful Increased mortality with longer followup. Increased kidney and liver injury, cardiac disorders.
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The Natural Stilbenoid (–)-Hopeaphenol Inhibits Cellular Entry of SARS-CoV-2 USA-WA1/2020, B.1.1.7, and B.1.351 Variants,
Antimicrobial Agents and Chemotherapy,
doi:10.1128/AAC.00772-21
Antivirals are urgently needed to combat the global SARS-CoV-2/COVID-19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding of the viral spike receptor binding domain (RBD) to the host angiotensin-converting enzyme II (ACE2) receptor may be effective inhibitors of SARS-CoV-2 cell entry.
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The pan-African natural products library compounds oleanolic acid, poinsettifolin B, and rhuschalcone III disrupt SARS-CoV-2 spike-host ACE2 interactions and SARS-CoV-2 replication,
BMC Pharmacology and Toxicology,
doi:10.1186/s40360-026-01264-3
Abstract Natural product (NP)-based chemical libraries are a rich source of antiviral compounds that can serve as the basis for new therapeutic leads to treat viral diseases, particularly for individuals lacking sustained access to existing vaccines and therapeutics. To identify new NP-based candidate inhibitors of SARS-CoV-2 cellular entry and viral replication, we screened the pan-African Natural Products Library (p-ANAPL), a collection of physical pure compounds obtained from African medicinal plants, for NPs that can disrupt the in vitro interaction of the SARS-CoV-2 Spike receptor-binding domain (RBD) with its host ACE2 entry receptor. This screen identified three compounds – oleanolic acid, poinsettifolin B, and rhuschalcone III – which disrupt RBD/ACE2 interactions with half-maximal inhibitory concentrations (IC 50 s) of 0.5–2.4 µM but do not disrupt an unrelated PD-1/PD-L1 host ligand/receptor binding pair. Oleanolic acid and rhuschalcone III, but not poinsettifolin B, additionally inhibited SARS-CoV-2 replication in Vero cells without cytotoxicity at low micromolar concentrations. Computational modelling indicated that all three compounds interact with numerous RBD and ACE2 residues, including a subset conserved across SARS-CoV-2 variants of concern. Taken together, we identify three NPs that selectively interfere with factors involved in SARS-CoV-2 entry and/or viral replication, representing new antiviral leads for COVID-19 management in resource-limited areas.