A Small Molecule That In Vitro Neutralizes Infection of SARS-CoV-2 and Its Most Infectious Variants, Delta, and Omicron

The COVID-19 pandemic has underscored the urgent need to develop highly potent and safe medications that are complementary to the role of vaccines. Specifically, it has exhibited the need for orally bioavailable broad-spectrum antivirals that are able to be quickly deployed against newly emerging viral pathogens. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and its variants Delta and Omicron are still a major threat to patients of all ages. In this brief report, we describe that the small molecule CD04872SC was able to neutralize SARS-CoV2 infection with a half-maximal effective concentration (EC50) = 248 μM. Serendipitously, we also were able to observe that CD04872SC inhibited the infection of the SARS-CoV-2 variants; Delta (EC50 = 152 μM) and Omicron (EC50 = 308 μM). These properties may define CD04872SC as a potential broad-spectrum candidate lead for the development of treatments for COVID-19.

[1]  D. Fremont,et al.  An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies , 2022, Nature Medicine.

[2]  L. Bekker,et al.  Effectiveness of BNT162b2 Vaccine against Omicron Variant in South Africa , 2021, The New England journal of medicine.

[3]  Elisabeth Mahase Covid-19: Pfizer’s paxlovid is 89% effective in patients at risk of serious illness, company reports , 2021, BMJ.

[4]  M. Buck,et al.  Neuropilin-1 assists SARS-CoV-2 infection by stimulating the separation of Spike protein S1 and S2 , 2021, Biophysical journal.

[5]  Deenadayalan Bakthavatsalam,et al.  Identification of Inhibitors of Integrin Cytoplasmic Domain Interactions With Syk , 2021, Frontiers in Immunology.

[6]  Zhaohui Zheng,et al.  CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells , 2020, Signal Transduction and Targeted Therapy.

[7]  A. Helenius,et al.  Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity , 2020, Science.

[8]  Shibo Jiang,et al.  Learning from the past: development of safe and effective COVID-19 vaccines , 2020, Nature Reviews Microbiology.

[9]  Fang Li,et al.  Cell entry mechanisms of SARS-CoV-2 , 2020, Proceedings of the National Academy of Sciences.

[10]  Linqi Zhang,et al.  Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor , 2020, Nature.

[11]  A. Walls,et al.  Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein , 2020, Cell.

[12]  J. Briggs,et al.  Inhibition of Cholera Toxin and Other AB Toxins by Polyphenolic Compounds , 2016, PloS one.

[13]  R. Mannhold,et al.  Calculation of molecular lipophilicity: state of the art and comparison of methods on more than 96000 compounds , 2009, Journal of pharmaceutical sciences.

[14]  J. Xing,et al.  Function of HAb18G/CD147 in Invasion of Host Cells by Severe Acute Respiratory Syndrome Coronavirus , 2005, The Journal of infectious diseases.

[15]  D. Koshland Application of a Theory of Enzyme Specificity to Protein Synthesis. , 1958, Proceedings of the National Academy of Sciences of the United States of America.