S-892216 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.
S-892216 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 S-892216 in detail.
, P-1079. In Vitro and in Vivo Antiviral Activity of S-892216, a Second-Generation Oral 3CLpro Inhibitor against SARS-CoV-2, Open Forum Infectious Diseases, doi:10.1093/ofid/ofae631.1267
Abstract Background COVID-19 caused by SARS-CoV-2 remains a global public health concern. Although oral direct-acting antivirals for COVID-19 (such as molnupiravir, nirmatrelvir/ritonavir, ensitrelvir) were approved for clinical use, there are concerns about drug-drug interactions (DDI) and safety, so development of new therapeutics is needed. In this study, we describe enzyme inhibitory and antiviral activity of S-892216, a second-generation small molecular 3C-like protease (3CLpro) inhibitor. Methods The 3CLpro enzymatic assay was conducted by mass spectrometry system. In vitro antiviral activity was evaluated using VeroE6/TMPRSS2 cells and human airway epithelial cells (hAEC) following infection by several SARS-CoV-2 variants. In vivo efficacy was evaluated using Balb/c mice, intranasally infected with SARS-CoV-2, and S-892216 was orally administered. Results S-892216 showed high 3CLpro inhibitory activity (IC50 = 0.697 nmol/L) and exhibited in vitro antiviral activity against several SARS-CoV-2 strains, including Omicron variants (EC50 = 2.27-12.5 nmol/L in VeroE6/TMPRSS2 cells, EC90 = 2.31-2.41 nmol/L in hAECs). Furthermore, S-892216 suppressed lung virus titer in Balb/c mice infected with SARS-CoV-2 in a dose-dependent manner. Conclusion S-892216 has stronger 3CLpro inhibitory and antiviral activity than approved 3CLpro inhibitors and has been confirmed to be effective in vivo. Due to the strong antiviral activity of S-892216, it is suggested to be effective at low doses in clinical settings. DDI and safety will be evaluated in clinical trials. Disclosures Haruaki Nobori, PhD, Shionogi & Co., Ltd.: Employee|Shionogi & Co., Ltd.: Stocks/Bonds (Private Company) Sho Kawashima, Shionogi & Co., Ltd.: Employee Reiko Dodo, n/a, Shionogi & Co., Ltd.: Employee Yuki Maruyama, PhD, Shionogi & Co., Ltd.: Employee|Shionogi & Co., Ltd.: Stocks/Bonds (Private Company) Takayo Haruna, n/a, Shionogi & Co., Ltd.: Employee Keiichiro Hirai, PhD, Shionogi & Co., Ltd.: Employee Yuto Unoh, PhD, Shionogi & Co., Ltd.: Employee Kenji Nakahara, PhD, Shionogi & Co., Ltd.: Employee Shota Uehara, Ph.D., Shionogi & Co., Ltd.: Employee|Shionogi & Co., Ltd.: Stocks/Bonds (Private Company) ryosuke watari, n/a, Shionogi & Co., Ltd.: Employee tomoyuki kawachi, n/a, Shionogi & Co., Ltd.: Employee yuka Natsume, n/a, Shionogi & Co., Ltd.: Employee katsumoto hata, n/a, Shionogi & Co., Ltd.: Employee yukiko orita, n/a, Shionogi & Co., Ltd.: Employee kae fujisawa, n/a, Shionogi & Co., Ltd.: Employee tetsuya miyano, PhD, Shionogi & Co., Ltd.: Employee hideko kaneda, n/a, Shionogi..
, 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.
, Selection of Solubility Enhancement Technologies for S-892216, a Novel COVID-19 Drug Candidate, Pharmaceutics, doi:10.3390/pharmaceutics17121627
Background/Objectives: S-892216 is a poorly water-soluble drug developed as a novel oral treatment for COVID-19, although its oral absorption is low. For Phase 1 (Ph1) studies and commercial use, both oral solution and solid dispersion technologies are evaluated to enhance drug solubility. Methods: The solubility enhancement technology was selected by considering physicochemical factors such as stability and oral absorption, along with patient and customer acceptability. Results: Pharmacokinetics study in rats revealed that both the polyethylene glycol 400 oral solution and polyvinylpyrrolidone-vinyl acetate (PVPVA) amorphous solid dispersion powder suspension showed almost 100% oral bioavailability. Therefore, they can be proposed as clinical formulations for Ph1 studies. PVPVA solid dispersion tablets were developed as a to-be-marketed formulation showed higher bioavailability in dogs than the anhydrous crystal formulation. Additionally, the stability of the developed solid dispersion tablet was acceptable. Conclusions: This study demonstrates that multiple solubility enhancement technologies can be adopted for S-892216 development, and amorphous solid dispersion technology was selected for commercialization.