Revealing the Mechanism of SARS-CoV-2 Spike Protein Binding With ACE2

Abstract

A large population in the world has been infected by COVID-19. Understanding the mechanisms of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is important for the management and treatment of COVID-19. When it comes to the infection process, one of the most important proteins in SARS-CoV-2 is the spike (S) protein, which is able to bind to human Angiotensin-Converting Enzyme 2 (ACE2) and initializes the entry of the host cell. In this study, we implemented multiscale computational approaches to study the electrostatic features of the interfaces of the SARS-CoV-2 S protein receptor binding domain and ACE2. The simulations and analyses were performed on highperformance computing resources in the Texas Advanced Computing Center. Our study identified key residues on SARS-CoV-2, which can be used as targets for future drug design. The results shed light on future drug design and therapeutic targets for COVID-19. & THE NUMBER OF confirmed cases of Coronavirus Disease 2019 (COVID-19) is increasing dramatically 1 due to the fast spread of SARS-CoV-2. The large coronavirus family includes hundreds of viruses that usually do not pose a threat to human health. SARS-CoV-2 is the seventh member of those coronaviruses that infect the human body. Of these, four (HCoV-229E, HCoV-OC43, HCoV-NL63, HKU1) 2 cause mild to moderate symptoms, while the other three can cause serious, even fatal diseases. SARS coronavirus (SARS-CoV) broke out in 2002 and caused Severe Acute Respiratory Syndrome (SARS). MERS coronavirus (MERS-CoV)

Identification of potential plant bioactive as SARS-CoV-2 Spike protein and human ACE2 fusion inhibitors

“…The visual analysis of docked complexes revealed that the Dicaffeoylquinic acid displayed maximum number of hydrogen bond with the residues responsible for significant role in binding. Previously published studies reported that the residues Lys417, Phe456, Gln493, Glu484, Tyr473, and Tyr489 of S-RBD interface majorly contributed in binding with ACE2 [ 7 , 9 , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] ]⁠. Moreover, in various in-silico studies, many phytochemicals (Bis-demethoxycurcumin, compound-4, compound-2, hesperidin, emodin, chrysin, nabiximols, pectolinarin, epigallocatechin gallate, rhoifolin, andrographolide, artemisinin, apigenin, berberine, emodin, capsaicin, glabridin, colchicine, harmaline, kaempferol, harmine, niranthin, phyllanthin, oleic acid, rosavin, withanolide A, withaferin A, curcumin, apigenin, and chrysophanol) were also recommended as S-RBD inhibitors on the basis of molecular docking studies [ [53] , [54] , [55] , [56] ]⁠.…”

Electrostatic features for nucleocapsid proteins of SARS-CoV and SARS-CoV-2

“…Thus, the N protein RBDs are attracted by RNAs because the two interfaces have opposite net charges. Such a phenomenon is common in the interactions between biomolecules [ 7 , 35 ]. The electrostatic features of N proteins and RNAs indicate that the electrostatic binding forces between N proteins and RNAs may enhance the stabilities of the complexes.…”

“…Compared with experimental studies, some effort has been also made to investigate SARS-CoV and SARS-CoV-2 using computational approaches. Most of these computational studies focused on the spike (S) proteins of the SARS-CoV and SARS-CoV-2 [ 7 , 8 ], including discoveries of potential drug targets for SARS-CoV-2 [ 9 - 11 ], few works focused on N proteins. Some studies calculated the electrostatic potential on N protein surfaces in coronavirus [ 3 , 5 , 6 ].…”

“…Due to the relatively high cost of experiments and the rapid development of computational algorithms [ 12 , 13 ], computational methods are now widely used to study biology phenomena, including biomolecular structures [ 14 , 15 ], biomolecular interactions [ 16 - 18 ], pH dependence of protein-protein/DNA/RNA interactions [ 19 , 20 ], etc. Using such state of art computing techniques, a lot of efforts have been contributed to study viruses [ 7 , 21 , 22 ]. In this work, several computational approaches are used to study nucleocapsid proteins of SARS-CoV and SARS-CoV-2, including DelPhi [ 23 ], DelPhiForce [ 24 , 25 ], DelPhiPKa [ 26 , 27 ].…”

Research on Data Science Ensembles for Covid-19 Detection and Length of Stay Prediction

“…Novel Coronavirus 2019 (Covid- 19) is a disease that pioneered in Hubei district in Wuhan city of China and has expanded globally. It is prompted by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [1]. Covid-19 was announced pandemic by the World Health Organization (WHO) on March 11, 2020.…”