CMX990 for COVID-19
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 25 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.
CMX990 may be beneficial for
COVID-19 according to the studies below.
COVID-19 involves the interplay of 500+ viral and host proteins and factors providing many therapeutic targets.
Scientists have proposed 11,000+ potential treatments.
c19early.org analyzes
220+ treatments.
We have not reviewed CMX990 in detail.
, Discovery of CMX990: A Potent SARS-CoV-2 3CL Protease Inhibitor Bearing a Novel Covalent Warhead, bioRxiv, doi:10.1101/2023.10.24.563688
ABSTRACTThere remains a need to develop novel SARS-CoV-2 therapeutic options that improve upon existing therapies by increased robustness of response, fewer safety liabilities, and global-ready accessibility. Functionally critical viral main protease (Mpro, 3CLpro) of SARS-CoV-2 is an attractive target due to its homology within the coronaviral family, and lack thereof towards human proteases. In this disclosure, we outline the advent of a novel SARS-CoV-2 3CLproinhibitor, CMX990, bearing an unprecedented trifluoromethoxymethyl ketone warhead. Compared with the marketed drug nirmatrelvir (combination with ritonavir = PaxlovidTM), CMX990 has distinctly differentiated potency (∼5x more potent in primary cells) and humanin vitroclearance (>4x better microsomal clearance and >10x better hepatocyte clearance), with goodin vitro-in vivocorrelation. Based on its compelling preclinical profile and projected once or twice a day dosing supporting unboosted oral therapy in humans, CMX990 advanced to a Phase 1 clinical trial as an oral drug candidate for SARS-CoV-2.
, Recent Advances in the Design of Inhibitors Targeting the Viral Entry and Replication of the SARS-CoV-2 Virus, Driven by In Silico Approaches, Molecules, doi:10.3390/molecules31162877
The SARS-CoV-2 pandemic has significantly impacted global health, politics, medicine, finance, and society. Since 2020, various mutations have been reported, leading to drug resistance in current treatments against different SARS-CoV-2 strains and a drastic increase in cases of long-COVID. This situation underscores the urgent need to develop targeted and effective drugs to combat the spread of SARS-CoV-2 strains and their mutants, manage long-COVID symptoms and prepare for future pandemics. Currently, the treatment of SARS-CoV-2 focuses on targeting the virus’s entry and replication mechanisms to disrupt its life cycle. This review examines approved drugs, clinical candidates, and inhibitors under development, along with their bioassay data, while highlighting associated challenges. It illustrates how inhibitors bind to active sites, providing insights and emphasizing the importance of in silico studies, such as molecular docking, molecular dynamics simulation, FEP+, WaterMap, and quantitative structure–activity relationship (QSAR) analyses, and their correlation with experimental studies in expediting the drug discovery process. The review aims to provide researchers with insights into the gaps that need to be addressed concerning mutations affecting viral entry and to prepare for future pandemics.