Query: comparison of spike proteins of MERS, SARS-CoV and SARS-CoV-2

title: Comprehensive Structural and Molecular Comparison of Spike Proteins of SARS CoV 2, SARS CoV and MERS CoV, and Their Interactions with ACE2
abstract: The severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) has recently emerged in China and caused a disease called coronavirus disease 2019  The virus quickly spread around the world, causing a sustained global outbreak. Although SARS CoV 2, and other coronaviruses, SARS CoV and Middle East respiratory syndrome CoV (MERS CoV) are highly similar genetically and at the protein production level, there are significant differences between them. Research has shown that the structural spike (S) protein plays an important role in the evolution and transmission of SARS CoV 2. So far, studies have shown that various genes encoding primarily for elements of S protein undergo frequent mutation. We have performed an in depth review of the literature covering the structural and mutational aspects of S protein in the context of SARS CoV 2, and compared them with those of SARS CoV and MERS CoV. Our analytical approach consisted in an initial genome and transcriptome analysis, followed by primary, secondary and tertiary protein structure analysis. Additionally, we investigated the potential effects of these differences on the S protein binding and interactions to angiotensin converting enzyme 2 (ACE2) and we established, after extensive analysis of previous research articles, that SARS CoV 2 and SARS CoV use different ends/regions in S protein receptor binding motif (RBM) and different types of interactions for their chief binding with ACE2. These differences may have significant implications on pathogenesis, entry and ability to infect intermediate hosts for these coronaviruses. This review comprehensively addresses in detail the variations in S protein, its receptor binding characteristics and detailed structural interactions, the process of cleavage involved in priming, as well as other differences between coronaviruses.

title: A Novel Vaccine Employing Non Replicating Rabies Virus Expressing Chimeric SARS CoV 2 Spike Protein Domains: Functional Inhibition of Viral/Nicotinic Acetylcholine Receptor Complexes
abstract: The emergence of the novel b coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) has resulted in a global pandemic of coronavirus disease 2019  Clinical studies have documented that potentially severe neurological symptoms are associated with SARS CoV 2 infection, thereby suggesting direct CNS penetration by the virus. Prior studies have demonstrated that the destructive neurological effects of rabies virus (RABV) infections are mediated by CNS transport of the virus tightly bound to the nicotinic acetylcholine receptor (nAChR) By comparison, it has been hypothesized that a similar mechanism exists to explain the multiple neurological effects of SARS CoV 2 via binding to peripheral nAChRs followed by orthograde or retrograde transport into the CNS. Genetic engineering of the RABV has been employed to generate novel vaccines consisting of non replicating RABV particles expressing chimeric capsid proteins containing human immunodeficiency virus 1 (HIV 1) Middle East respiratory syndrome (MERS CoV) Ebolavirus, and hepatitis C virus (HCV) sequences. Accordingly, we present a critical discussion that integrates lessons learned from prior RABV research and vaccine development into a working model of a SARS CoV 2 vaccine that selectively targets and neutralizes CNS penetration of a tightly bound viral nAChR complex.

title: The Comparison of SARS CoV 2, SARS CoV, and MERS CoV Genome and Spike Protein Variations
abstract: SARS CoV 2 is a virus that has caused COVID 19 pandemic. This virus is a new variant of the SARS CoV virus and also closely related to MERS CoV, which caused similar acute respiratory infections. All these viruses recognize target cells by binding to the Receptor Binding Domain (RBD) on Spike protein with receptors. This study aimed to determine the SARS CoV 2, MERS CoV, and SARS CoV genome structure, Spike protein sequence differences, and variations of RBD's Receptor Binding Motif (RBM) This research was using data mining approach. Genome sequences were downloaded from NCBI, except for Indonesian samples were downloaded from GISAID. Genomic structures, Spike sequence, and RBD structure were analyzed using Bioedit, followed by protein modelling using SwissModel and PyMol applications. The result showed that the SARS CoV 2, MERS CoV, and SARS CoV genome shared the same genes yet in different numbers and length. SARS CoV 2 Spike protein sequence was quite similar to SARS CoV Spike protein, but very different to the Spike protein of MERS CoV. There were variations of RBD's RBM structure due to the mutations occurred among these viruses. It is suggested that these differences may increase the affinity between SARS CoV 2 Spike protein to its hACE2 receptor which caused SARS CoV 2 becomes more infective and spread wider than SARS CoV and MERS CoV, in turn. This result expected to be basic information for the development of SARS CoV 2 introduction inhibition agent and spreading prevention.

title: Spike Proteins of SARS CoV and SARS CoV 2 Utilize Different Mechanisms to Bind With Human ACE2
abstract: The ongoing outbreak of COVID 19 has been a serious threat to human health worldwide. The virus SARS CoV 2 initiates its infection to the human body via the interaction of its spike (S) protein with the human Angiotensin Converting Enzyme 2 (ACE2) of the host cells. Therefore, understanding the fundamental mechanisms of how SARS CoV 2 S protein receptor binding domain (RBD) binds to ACE2 is highly demanded for developing treatments for COVID 19. Here we implemented multi scale computational approaches to study the binding mechanisms of human ACE2 and S proteins of both SARS CoV and SARS CoV 2. Electrostatic features, including electrostatic potential, electric field lines, and electrostatic forces of SARS CoV and SARS CoV 2 were calculated and compared in detail. The results demonstrate that SARS CoV and SARS CoV 2 S proteins are both attractive to ACE2 by electrostatic forces even at different distances. However, the residues contributing to the electrostatic features are quite different due to the mutations between SARS CoV S protein and SARS CoV 2 S protein. Such differences are analyzed comprehensively. Compared to SARS CoV, the SARS CoV 2 binds with ACE2 using a more robust strategy: The electric field line related residues are distributed quite differently, which results in a more robust binding strategy of SARS CoV 2. Also, SARS CoV 2 has a higher electric field line density than that of SARS CoV, which indicates stronger interaction between SARS CoV 2 and ACE2, compared to that of SARS CoV. Key residues involved in salt bridges and hydrogen bonds are identified in this study, which may help the future drug design against COVID 19.

title: Critical Differences between the Binding Features of the Spike Proteins of SARS CoV 2 and SARS CoV
abstract: The COVID 19 caused by SARS CoV 2 has spread globally and caused tremendous loss of lives and properties, and it is of utmost urgency to understand its propagation process and to find ways to slow down the epidemic. In this work, we used a coarse grained model to calculate the binding free energy of SARS CoV 2 or SARS CoV to their human receptor ACE2. The investigation of the free energy contribution of the interacting residues indicates that the residues located outside the receptor binding domain are the source of the stronger binding of the novel virus. Thus, the current results suggest that the essential evolution of SARS CoV 2 happens remotely from the binding domain at the spike protein trimeric body. Such evolution may facilitate the conformational change and the infection process that occurs after the virus is bound to ACE2. By studying the binding pattern between SARS CoV antibody m396 and SARS CoV 2, it is found that the remote energetic contribution is missing, which might explain the absence of cross reactivity of such antibodies.

title: Comparison of the COVID 2019 (SARS CoV 2) pathogenesis with SARS CoV and MERS CoV infections
abstract: The severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) was first identified in several patients who traveled to Wuhan or went to a seafood wholesale market in Wuhan. The phylogenetic tree showed that SARS CoV 2 was 96.2% identical to bat b coronaviruses from lineage B. Also, several studies reported that SARS CoV 2 uses the SARS CoV receptor, angiotensin converting enzyme 2, for entry to target cells. Lung alveolar and small intestine are potential targets for SARS CoV 2 due to the high expression of the angiotensin converting enzyme 2 receptor. In this review, we focused on the zoonotic b coronaviruses and given there is no specific drug or vaccine for coronavirus disease 2019, we reviewed the literature on the therapy options for SARS and Middle East respiratory syndrome coronavirus infection, in order to discover their possible use in the treatment of SARS CoV 2 infections.

title: Comparison of the SARS CoV 2 (2019 nCoV) M protein with its counterparts of SARS CoV and MERS CoV species
abstract: Coronaviruses M proteins are well represented in the major protein component of the viral envelope. During the viral assembly, they play an important role by association with all other viral structural proteins. Despite their crucial functions, very little information regarding the structures and functions of M proteins is available. Here we utilize bioinformatic tools from available sequences and 3D structures of SARS CoV, SARS CoV2, and MERS CoV M proteins in order to predict potential B cell epitopes and assessing antibody binding affinity. Such study aims to aid finding more effective vaccines and recognize neutralizing antibodies. we found some rather exciting differences between SARS COV 2, SARS Cov and MERS CoV M proteins. Two SARS CoV 2 peptides with significant antigen presentation scores for human cell surface proteins have been identified. The results reveal that N terminal domains of M proteins of SARS CoV and SARS CoV2 are translocated (outside) whereas it is inside (cytoplasmic side) in MERS CoV.

title: Mutation Hot Spots in Spike Protein of SARS CoV 2 Virus
abstract: Spike (S) protein of Corona viruses help in receptor attachment and virus entry into the host cells While S protein is required for virus entry, it is also important as an immunogen as it is the most accessible part of the virus architecture S protein form knob like structures (viral spikes) protruding outwards in the form of homotrimers containing an S1 and S2 as monomers Mutations in structural proteins of virus play crucial role in determining virulence and also in many instances influencing emergence of antibody escape variants and cellular tropism In this paper we have performed in depth analyses of spike protein sequences from various parts of the world and tried to correlate the data with possible functional relevance of such mutations

title: Identification of common deletions in the spike protein of SARS CoV 2.
abstract: SARS CoV 2 is a novel coronavirus first identified in December 2019. Notable features make SARS CoV 2 distinct from most other previously identified Betacoronaviruses, including the receptor binding domain of SARS CoV 2 and a unique insertion of twelve nucleotide or four amino acids (PRRA) at the S1/S2 boundary. In this study, we identified two deletion variants of SARS CoV 2 that either directly affect the polybasic cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN) These deletions were verified by multiple sequencing methods. In vitro results showed that the deletion of NSPRRAR likely does not affect virus replication in Vero and Vero E6 cells, however the deletion of QTQTN may restrict late phase viral replication. The deletion of QTQTN was detected in 3 of 68 clinical samples and half of 24 in vitro isolated viruses, whilst the deletion of NSPRRAR was identified in 3 in vitro isolated viruses. Our data indicate that (i) there may be distinct selection pressures on SARS CoV 2 replication or infection in vitro and in vivo, (ii) an efficient mechanism for deleting this region from the viral genome may exist, given that the deletion variant is commonly detected after two rounds of cell passage, and (iii) the PRRA insertion, which is unique to SARS CoV 2, is not fixed during virus replication in vitro These findings provide information to aid further investigation of SARS CoV 2 infection mechanisms and a better understanding of the NSPRRAR deletion variant observed here.Important notes The spike protein determines the infectivity and host range of coronaviruses. SARS CoV 2 has two unique features in its spike protein, the receptor binding domain and an insertion of twelve nucleotides at the S1/S2 boundary resulting a furin like cleavage site. Here, we identified two deletion variants of SARS CoV 2 that either directly affect the furin like cleavage site itself (NSPRRAR) or a flanking sequence (QTQTN) and investigated these deletions in cell isolates and clinical samples. The absence of the polybasic cleavage site in SARS CoV 2 did not affect virus replication in Vero or Vero E6 cells. Our data indicate the PRRAR and its flanking sites are not fixed in vitro, thus there appears to be distinct selection pressures on SARS CoV 2 sequences in vitro and in vivo Further investigation of the mechanism of generating these deletion variants and their infectivity in different animal models would improve our understanding of the origin and evolution of this virus.

title: Novel mutations in the spike protein of SARS CoV 2 from Bangladesh
abstract: Genetic characterization may provide useful insights into severe acute respiratory coronavirus 2 (SARS CoV 2) circulating in Bangladesh. Here we analyzed the SARS Cov 2 positive 41 nasopharyngeal samples collected in lysis buffer obtained at different regional national laboratories of Bangladesh during July December 2020. Full length spike gene was amplified and SARS CoV 2 was confirmed upon Sanger sequencing. Multiple  alignment and phylogenetic study of 15 strains showed that genetically diverse SARS CoV 2 is circulating in the country where 80 documented and 55 novel substitutions have been observed in different regions of spike glycoprotein. Major mutations and/or deletions was identified at conserved amino acid positions that are functionally linked to host transition, antigenic drift, host surface receptor binding or antibody recognition sites, and viral oligomerization interfaces that may have significant effects on pathogenic capacity and epidemiological signatures.