Abstract
Contributing to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical treatment, a drug library encompassing approximately 3,142 clinical-stage or FDA-approved small molecules is profiled to identify the candidate therapeutic inhibitors targeting nucleocapsid protein (N) and spike protein (S) of SARS-CoV-2.
16 screened candidates with higher binding affinity are evaluated via virtual screening. Comparing to those under trial/temporarily used antivirus drugs (i.e., umifenovir, lopinavir), ceftriaxone, cefotaxime, and cefuroxime show higher binding affinities to the N-terminal domain of N protein (N-NTD), C-terminal domain of N protein (N-CTD), and receptor-binding domain of S protein (S-RBD). Cefotaxime and cefuroxime have high binding affinities towards S-RBD with angiotensin-converting enzyme 2 (ACE2) complex via influence the critical interface sites at the interface of S-RBD (Arg403, Tyr453, Trp495, Gly496, Phe497, Asn501and Tyr505) and ACE2 (Asn33, His34, Glu37, Asp38, Lys353, Ala386, Ala387, Gln388, Pro389, Phe390 and Arg393) complex.
【저자키워드】 SARS-CoV-2, Antiviral compounds, Drug screen and repurposing, Small molecule microarray chip, 【초록키워드】 ACE2, coronavirus, S protein, Virtual screening, angiotensin-converting enzyme 2, binding affinity, Spike protein, nucleocapsid protein, S-RBD, therapeutic, N protein, small molecule, umifenovir, inhibitor, Critical, N-terminal domain, C-terminal domain, Clinical treatment, acute respiratory syndrome, complex, domain, candidate, drug library, identify, evaluated, screened, antivirus drug, Cefotaxime, 【제목키워드】 Spike protein, antiviral drug, SARS-CoV-2 nucleocapsid,