Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected the lives and livelihood of millions of individuals around the world. It has mutated several times after its first inception, with an estimated two mutations occurring every month. Although we have been successful in developing vaccines against the virus, the emergence of variants has enabled it to escape therapy. Few of the generated variants are also reported to be more infectious than the wild-type (WT). In this study, we analyze the attributes of all RBD/ACE2 complexes for the reported VOCs, namely, Alpha, Beta, Gamma, and Delta through computer simulations. Results indicate differences in orientation and binding energies of the VOCs from the WT. Overall, it was observed that electrostatic interactions play a major role in the binding of the complexes. Detailed residue level energetics revealed that the most prominent changes in interaction energies were seen particularly at the mutated residues which were present at RBD/ACE2 interface. We found that the Delta variant is one of the most tightly bound variants of SARS-CoV-2 with dynamics similar to WT. The high binding affinity of RBD towards ACE2 is indicative of an increase in viral transmission and infectivity. The details presented in our study provide additional information for the design and development of effective therapeutic strategies for the emerging variants of the virus in the future.
Keywords: Angiotensin-converting enzyme 2; Delta; Molecular dynamics; Receptor binding domain; SARS-CoV-2.
【저자키워드】 Delta, molecular dynamics, angiotensin-converting enzyme 2, SARS-CoV-2., Receptor binding domain, 【초록키워드】 SARS-CoV-2, ACE2, Vaccine, therapy, Mutation, VoC, variant, molecular dynamics, severe acute respiratory syndrome Coronavirus, delta variant, virus, angiotensin-converting enzyme 2, coronavirus 2, variants, binding affinity, binding energy, Receptor binding domain, Severe acute respiratory syndrome, RBD, VOCs, Gamma, Alpha, Beta, Viral transmission, respiratory, information, therapeutic strategy, binding, Angiotensin-converting enzyme, electrostatic interactions, Interaction, angiotensin, Orientation, Complexes, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, enzyme, individual, residue, wild-type, attributes, attribute, ACE2 complexes, variants of SARS-CoV-2, electrostatic interaction, effective, Result, affected, reported, changes in, increase in, mutated, complexes, 【제목키워드】 SARS-CoV-2 variant,