key: cord-1023260-egpz6blx authors: Sanches, Paulo.R.S.; Charlie-Silva, Ives; Braz, Helyson.L.B.; Bittar, Cintia; Calmon, Marilia; Rahal, Paula; Cilli, Eduardo M. title: Recent advances in SARS-CoV-2 Spike protein and RBD mutations comparison between new variants Alpha (B.1.1.7, United Kingdom), Beta (B.1.351, South Africa), Gamma (P.1, Brazil) and Delta (B.1.617.2, India) date: 2021-09-16 journal: J Virus Erad DOI: 10.1016/j.jve.2021.100054 sha: 5f41eb451944af68c9c750aef431262647301b80 doc_id: 1023260 cord_uid: egpz6blx New variants of SARS-CoV-2 Alpha (B.1.1.7); Beta (B.1.351) Gamma (P.1) and Delta (B.1.617.2) quickly spread in the UK, South Africa, Brazil and India, respectively. To address whether mutations in SARS-CoV-2 RBD spike protein could affect virus infectivity, peptides containing RBD amino acids mutations have been constructed and interacted with human ACE2 by computational methods. Our results suggest that mutations in RBD amino acids K417, E484, L452, T478 and N501 are expressively increasing the affinity of this protein with human angiotensin-converting enzyme 2 (ACE2), consequently variants Alpha (B.1.1.7), Beta (B1.351), Gamma (P.1) and Delta (B.1.617.2) could be more infective in human cells compared with SARS-CoV-2 isolated in Wuhan-2019 and the Gamma and Delta variants could be the most infective among them. In 2002-2003, the outbreak of severe acute respiratory syndrome occurred due to SARS-CoV in the Guangdong Province of China and quickly spread to twenty-seven countries [1] [2] [3] . One decade later, in 2012, MERS-CoV caused a severe respiratory disease that emerged in the Middle East with 2494 confirmed cases of human infection and 858 deaths [4] [5] [6] [7] . The rate of human-tohuman transmission of SARS-CoV-2 is higher than earlier outbreaks of Coronavirus via cough and/or sneezing droplets emitted from infected people 1,8 . Due to this rapid spreading and no efficient repairing mechanisms for RNA mutations, SARS-CoV-2 is susceptible to several and constant mutations. Notably, a single SARS-CoV amino acid change, Spike D480A/G in the receptor binding domain (RBD), arose in infected humans and civets and became the dominant variant among 2003/2004 viruses. SARS-CoV-2 is a positive singlestranded RNA virus whose genome encodes four structural proteins: spike (S), small protein (E), matrix (M), and nucleocapsid (N). The Spike protein is a type I fusion protein that forms trimers on the surface of the virion 9,10,11,12-14 . It is composed of two subunits, with S1 responsible for receptor binding and S2 for membrane fusion. SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as the receptor for entry into target cells [15] [16] [17] [18] [19] [20] [21] [22] [23] . Therefore, the S protein determines the infectivity of the virus and its transmissibility in the host. According to several studies, receptor binding domain (RBD) from Spike protein of SARS-CoV-2 contain six most important amino acids residues (L455, F486, Q493, S494, N501, and Y505) that mediate virus entry into the host cells 12, 14, 17, [26] [27] [28] [29] [30] [31] . However, mutations in other amino acids from Spike protein (S) could affect virus infection despite his interaction with human ACE2. Understanding the effect of amino acid substitutions in S protein from new variants comparing the strains on the transmissibility and virulence of SARS-CoV-2 is of broad and immediate interest. In the present study, we assess the impact of the RBD associated amino We performed our analyses using the crystallographic models of the SARS-CoV-2 Spike protein available in Protein Data Bank (PDBID 6LZG) and PyMol software to analyses the structures. PDB peptides sequences have been built with Swiss Model on line software and 3D structures constructed by PyMol. Docking analyses was performed by ClusPro 2.0 24, 25 . Using the crystal structure from Human ACE2-SARS-CoV-2 S protein deposited in Protein Data Bank (PDBID 6LZG - Figure 1 ) and the genome sequence from SARS-CoV-2 (NC_045512.2) we identified and aligned amino acids residues and 3D structures has been built from all mentioned strains ( Figure 2 Epidemiology, transmission dynamics and control of SARS: The 2002-2003 epidemic Encyclopedia of Environmental Health Middle East respiratory syndrome Middle East respiratory syndrome COVID-19, SARS and MERS: are they closely related? 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