Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus, and the most recent SARS-CoV-2 can replicate within the lower respiratory tract, causing a pneumonia that can be fatal [1, 6]. SARS-CoV-2 is responsible for the GNE-900 current COVID-19 pandemic that has spread to 218 countries, infecting more than 140 million people and causing more than 3 million deaths (WHO). ACE2 including S477N, N439K, V367F, and N501Y and address the potential impact of RBD mutations on antibody binding. The high frequency S477N mutation is present in 6.7% of all SARS-CoV-2 sequences, co-occurs with D614G, and is currently present in 14 countries. To address RBD-antibody interactions, we take a subset of human-derived antibodies and define their interacting residues using PDBsum. Our analysis shows that RBD mutations were found in approximately 9% of our dataset, with some mutations improving RBD-ACE2 interactions. We also show that antibody-mediated immunity against SARS-CoV-2 enlists broad coverage of the RBD, with Rabbit Polyclonal to RPL39L multiple antibodies targeting a variety of RBD regions. These data suggest that it is unlikely for neutralization/RBD antibody binding to be significantly impacted, as a whole, in the presence of RBD point mutations that conserve the RBD structure. Keywords: COVID-19, SARS-CoV-2, bioinformatics, receptor-binding domain name, mutations, antigenic evolution Statement of Significance SARS-CoV2 GNE-900 is responsible for the current COVID-19 pandemic. In this work, we developed a MATLAB program to analyze SARS-CoV-2 RBD mutations and conducted a thorough analysis of all SARS-CoV-2 RBD mutations using the GISAID database. We found four high frequency variants with improved binding to ACE2S477N, N439K, V367F, and N501Y and cross-referenced antibody conversation data with RBD mutations. INTRODUCTION Coronaviruses encompass a large family of viruses that can infect both humans and animals. To date, there are seven coronaviruses that are known to infect humans, causing relatively moderate to severe respiratory infections. Human coronaviruses 229E, NL63, OC43, and HKU1 typically replicate within the upper respiratory tract, resulting in infections that resemble the common cold [1C5]. Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus, and the most recent SARS-CoV-2 can replicate within the lower respiratory tract, causing a pneumonia that can be fatal [1, 6]. SARS-CoV-2 is responsible for the current COVID-19 pandemic that has spread to 218 countries, infecting more than 140 million people and causing more than 3 million deaths (WHO). This computer virus can be transmitted through respiratory droplets and is most commonly characterized by fever and cough but is also associated with pulmonary embolisms, kidney injury, and gastrointestinal symptoms [7C11]. Importantly, SARS-CoV-2 has a high transmission efficiency and can lead to mortality, especially when infecting the elderly or individuals with underlying medical conditions [12, 13]. Upon entry into the respiratory tract, coronaviruses use a homotrimeric spike glycoprotein (S protein) on the surface of the virion to mediate an conversation with the host receptor angiotensin-converting enzyme 2 (ACE2) and the protease TMPRSS2 [14, 15]. These interactions facilitate viral envelope fusion to the cell membrane via the endosomal pathway [16, 17]. The release of (+) sense RNA into the host cytoplasm allows for viral RNA translation and replication. Viral proteins and genomic RNA are subsequently assembled into virions and released from cells via vesicle transport. This infectious cycle causes host cells to undergo inflammatory pyroptotic cell GNE-900 death resulting in an aggressive inflammatory response and damage to the airways [1]. The S glycoprotein is essential for the initial conversation and internalization of the SARS-CoV-2 computer virus by the host making it an important structure around the virion [18C21]. The S protein is composed of the S1 and S2 domains with S1 made up of the receptor-binding domain (RBD) that directly interacts with the peptidase domain (PD) of the ACE2 protein (Fig. 1a and b). The S2 domain name contains a fusion peptide, two heptad repeats, a transmembrane region, and an intracellular region (Fig. 1a). RBD-mediated receptor binding causes dissociation of the S1 domain name and allows for the S2 domain name to reach a post-fusion state enabling viral membrane fusion [16, 17]. Open in a.