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1.
Heliyon ; : e12650, 2022.
Article in English | ScienceDirect | ID: covidwho-2165328

ABSTRACT

Circulation of the Omicron variant with the reemergence of the N501Y mutation along with many others in the spike protein has once again stirred the academic community. Interestingly, tracing the genetic diversity of SARS-CoV-2 shed light on a less frequent N501Y+ Delta variant which has been in the global circulation for some time before the Omicron appearance. This paper aims to present the molecular characteristics of the SARS-CoV-2 Spike_N501Y+ Delta variant detected in Bosnia and Herzegovina. The study was conducted during November and December 2021. All patients were tested using real-time RT-PCR for detection of SARS-CoV-2. A representative number of SARS-CoV-2 positive samples was pre-screened using VirSNiP SARS-CoV-2 Spike N501Y kit. The characterization of the viruses was carried out with Illumina RNA Prep with enrichment and the Respiratory Virus Oligo Panel kit. Among the analyzed sequences, we found two isolates of the Delta variant that differ from their most related clade- GK AY.4.3 in additional mutations N501Y and L54F. In this study, we described the presence of a rare form of Delta variant with Spike_N501Y mutation in the shadow of the Omicron emergence. Despite the set of mutations in the Spike protein, this form of Delta variant does not indicate the large-scale consequences for the general population. Further functional studies of this form could provide more information about its antigenicity and infectivity.

2.
Gene ; : 147144, 2022.
Article in English | ScienceDirect | ID: covidwho-2165309

ABSTRACT

Background SARS-CoV-2 has a significant impact on healthcare systems all around the world. Due to its high pathogenicity, live SARS-CoV-2 must be handled under biosafety level 3 conditions. Pseudoviruses are useful virological tools because of their safety and versatility, but the low titer of these viruses remains a limitation for their more comprehensive applications. Method Here, we constructed a Luc/eGFP based on a pseudotyped lentiviral HIV-1 system to transduce SARS-CoV-2 S glycoprotein to detect cell entry properties and cellular tropism. Results The furin cleavage site deletion of the S protein removed (SFko) can help SARS-CoV-2 S to be cleaved during viral packaging to improve infection efficiency. The furin cleavage site in SARS-CoV-2-S mediates membrane fusion and SFko leads to an increased level of S protein and limits S1/S2 cleavage to enhance pseudovirus infection in cells. Full-length S (SFL) pseudotyped with N, M, and E helper packaging can effectively help SFL infect cells. Finally, pseudotyped SFko particles were successfully used to detect neutralizing antibodies in RBD protein-immunized mouse serum. Conclusion Overall, our study indicates a series of modifications that result in the production of relatively high-titer SARS-COV-2 pseudo-particles that may be suitable for the detection of neutralizing antibodies from COVID-19 patients.

3.
Developmental & Comparative Immunology ; 140:104626, 2023.
Article in English | ScienceDirect | ID: covidwho-2165211

ABSTRACT

One of the most studied defense mechanisms against invading pathogens, including viruses, are Toll-like receptors (TLRs). Among them, TLR3, TLR7, TLR8 and TLR9 detect different forms of viral nucleic acids in endosomal compartments, whereas TLR2 and TLR4 recognize viral structural and nonstructural proteins outside the cell. Although many different TLRs have been shown to be involved in SARS-CoV-2 infection and detection of different structural proteins, most studies have been performed in vitro and the results obtained are rather contradictory. In this study, we report using the unique advantages of the zebrafish model for in vivo imaging and gene editing that the S1 domain of the Spike protein from the Wuhan strain (S1WT) induced hyperinflammation in zebrafish larvae via a Tlr2/Myd88 signaling pathway and independently of interleukin-1β production. In addition, S1WT also triggered emergency myelopoiesis, but in this case through a Tlr2/Myd88-independent signaling pathway. These results shed light on the mechanisms involved in the fish host responses to viral proteins.

4.
Biomedicine & Pharmacotherapy ; 158:114213, 2023.
Article in English | ScienceDirect | ID: covidwho-2165109

ABSTRACT

The rapid emergence of highly transmissible SARS-CoV-2 variants poses serious threat to the efficacy of vaccines and neutralizing antibodies. Thus, there is an urgent need to develop new and effective inhibitors against SARS-CoV-2 and future outbreaks. Here, we have identified a series of glycopeptide antibiotics teicoplanin derivatives that bind to the SARS-CoV-2 spike (S) protein, interrupt its interaction with ACE2 receptor and selectively inhibit viral entry mediated by S protein. Computation modeling predicts that these compounds interact with the residues in the receptor binding domain. More importantly, these teicoplanin derivatives inhibit the entry of both pseudotyped SARS-CoV-2 Delta and Omicron variants. Our study demonstrates the feasibility of developing small molecule entry inhibitors by targeting the interaction of viral S protein and ACE2. Together, considering the proven safety and pharmacokinetics of teicoplanin as a glycopeptide antibiotic, the teicoplanin derivatives hold great promise of being repurposed as pan-SARS-CoV-2 inhibitors.

5.
Antiviral Research ; 209:105509, 2023.
Article in English | ScienceDirect | ID: covidwho-2165064

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a threat to global public health, underscoring the urgent need for the development of preventive and therapeutic measures. The spike (S) protein of SARS-CoV-2, which mediates receptor binding and subsequent membrane fusion to promote viral entry, is a major target for current drug development and vaccine design. The S protein comprises a large N-terminal extracellular domain, a transmembrane domain, and a short cytoplasmic tail (CT) at the C-terminus. CT truncation of the S protein has been previously reported to promote the infectivity of SARS-CoV and SARS-CoV-2 pseudoviruses. However, the underlying molecular mechanism has not been precisely elucidated. In addition, the CT of various viral membrane glycoproteins play an essential role in the assembly of virions, yet the role of the S protein CT in SARS-CoV-2 infection remains unclear. In this study, through constructing a series of mutations of the CT of the S protein and analyzing their impact on the packaging of the SARS-CoV-2 pseudovirus and live SARS-CoV-2 virus, we identified V1264L1265 as a new intracellular targeting motif in the CT of the S protein, that regulates the transport and subcellular localization of the spike protein through the interactions with cytoskeleton and vesicular transport-related proteins, ARPC3, SCAMP3, and TUBB8, thereby modulating SARS-CoV-2 pseudovirus and live SARS-CoV-2 virion assembly. Either disrupting the V1264L1265 motif or reducing the expression of ARPC3, SCAMP3, and TUBB8 significantly repressed the assembly of the live SARS-CoV-2 virion, raising the possibility that the V1264L1265 motif and the host responsive pathways involved could be new drug targets for the treatment of SARS-CoV-2 infection. Our results extend the understanding of the role played by the S protein CT in the assembly of pseudoviruses and live SARS-CoV-2 virions, which will facilitate the application of pseudoviruses to the study of SARS-CoV-2 and provide potential strategies for the treatment of SARS-CoV-2 infection.

6.
Journal of Chromatography B ; : 123579, 2022.
Article in English | ScienceDirect | ID: covidwho-2165505

ABSTRACT

Recombinant SARS-CoV-2 trimeric spike protein produced by mammalian cell culture is a potential candidate for a COVID-19 vaccine. However, this protein is much larger than most typical biopharmaceutical proteins and its large-scale manufacture is therefore challenging. Particularly, its purification using resin-based chromatography is difficult as the diffusive transport of this protein to and from its binding site within the pores of the stationary phase particles is slow. Therefore, very low flow rates need to be used during binding and elution, and this slows down the purification process. Also, due to its large size, the binding capacity of this protein on resin-based media is low. Membrane chromatography is an efficient and scalable technique for purifying biopharmaceuticals. The predominant mode of solute transport in a membrane is convective and hence it is considered better than resin-based chromatography for purifying large proteins. In this paper, we propose a membrane chromatography-based purification method for fast and scalable manufacture of recombinant SARS-CoV-2 trimeric spike protein. A combination of cation exchange z2 laterally-fed membrane chromatography and size exclusion chromatography was found to be suitable for obtaining a homogeneous spike protein sample from mammalian cell culture supernatant. The proposed method is both fast and scalable and could be explored as a method for manufacturing vaccine grade spike protein.

7.
Curr Drug Targets ; 2022 Oct 14.
Article in English | MEDLINE | ID: covidwho-2162792

ABSTRACT

BACKGROUND: SARS-CoV2 is the causative virus for the CoVID-19 pandemic that has frequently mutated to continue to infect and resist available vaccines. Emerging new variants of the virus have complicated notions of immunity conferred by vaccines versus immunity that results from infection. While we continue to progress from epidemic to endemic as a result of this collective immunity, the pandemic still remains a morbid and mortal problem. OBJECTIVE: The SARS-CoV2 virus has a very complex manner of replication. The Spike Protein, one of the four structural proteins of the encapsulated virus, is central to the ability of the virus to penetrate cells in order to replicate. The objective of this review is to summarize these complex features of viral replication. METHODS: A review of the recent literature on the biology of SARS-CoV2 infection from published work from PubMed as well as work reported to preprint servers, e.g., bioRxiv, medRxiv. RESULTS AND CONCLUSION: The complex molecular and cellular biology involved in SARS-CoV2 replication and the origination of >30 proteins from a single open reading frame (ORF) have been summarized, as well as the structural biology of Spike Protein, a critical factor in cellular entry of the virus which is a necessary feature for it to replicate and cause disease.

8.
Pediatrics ; 150, 2022.
Article in English | ProQuest Central | ID: covidwho-2162657

ABSTRACT

PURPOSE OF THE STUDY: To investigate the role of the mucosal immune system of the upper respiratory tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by exploration of the presence of pre-existing mucosal SARS-CoV-2-reactive B cells in tonsillar tissue specimens. STUDY POPULATION: Tonsillar tissue from pediatric patients who underwent tonsillectomy at The Hospital for Sick Children in Toronto, Canada in 2015 to 2016, before the COVID-19 pandemic. METHODS: Using flow cytometry and fluorescently labeled tetramers to the SARS-CoV-2 Spike protein (S-protein), SARS-CoV-2-reactive B cells were isolated from tonsillar tissue. Monoclonal antibodies (mAbs) recognizing the SARS-CoV-2 S-protein were generated from these B-cells using single-cell real time-polymerase chain reaction and RNA sequencing. Human embryonic kidney derived cell lines expressing SARS-CoV-2 S protein were used for in vitro assays assessing the mAbs' SARS-CoV-2 recognition and Ag binding. RESULTS: Pre-existing SARS-CoV-2-reactive B cells were identified and isolated from prepandemic human tonsillar tissue. The mAbs generated from these B cells recognized the S-protein of the wild-type SARS-CoV-2 virus. Additionally, the mAbs originated from naïve B cells as well as Ag-experienced memory B cells, germinal center B cells, and plasma cells. These mAbs were able to partially block binding in vitro by consistently showing >20% inhibition of S-protein binding. The antibodies did not react to the S-proteins of endemic coronaviruses, human coronavirus-OC43 and human coronavirus-229E. The antibodies also demonstrated significantly reduced recognition of the SARS-CoV-2 B.1.1.7 and B1.315 variants. CONCLUSIONS: B cells contained in the lymphoid tissues of the upper respiratory tract can contain pre-existing SARS-CoV-2 reactive antibodies. Monoclonal antibodies generated by these B-cells demonstrated in vitro SARS-CoV-2 recognition and neutralizing potential. However, these mAbs had reduced binding to the Spike proteins of SARS-CoV-2 variants and did not recognize endemic coronaviruses. The existence of these antibodies may explain the variation in COVID-19 symptom severity since these pre-existing Abs may lead to rapid engagement of the SARS-CoV-2 pathogen as the mucosal surface of the respiratory tract is a main point of contact.

9.
Lab Med ; 2022.
Article in English | PubMed | ID: covidwho-2161108

ABSTRACT

OBJECTIVE: Patients and physicians are increasingly requesting their clinical laboratory to provide SARS-CoV-2 serology interpretation. Our study aimed to assess the evolution of SARS-CoV-2 antibodies in Moderna-vaccinated health care workers. METHODS: We analyzed the evolution of mRNA-1273 (Moderna)-elicited antibodies by 2 high-throughput assays, TrimericS IgG (Diasorin) and SARS-CoV-2 IgG-II (Abbott). RESULTS: After the first injection, the COVID-19-recovered vaccinees showed a serological response as strong as that observed 1 month after the second injection in participants without COVID-19 history. Although remaining above the positivity thresholds, the TrimericS immunoglobulin G (IgG) and anti-RBD (receptor-binding domain) IgG levels fell considerably between 1 and 7 months postvaccination, dropping to 10.6% and 13% for the COVID-19 recovered subgroup and to 11.7% and 9.3% for the COVID-19 naive subgroup. CONCLUSION: Regardless of the test used, a decrease in circulating anti-SARS-CoV-2 IgG levels should be expected a few months after vaccination. As this decline does not preclude the efficacy of immune response, caution is necessary when interpretating postvaccination serological data.

10.
ACS Symposium Series ; 1429:145-164, 2022.
Article in English | Scopus | ID: covidwho-2160152

ABSTRACT

Best Practices for Undergraduate Student Research Programs. This book brings to light the important research and training that takes place at predominantly undergraduate institutions (PUIs). The purpose of this work is threefold: to disseminate important physical chemistry results to the chemistry and physics communities;to demonstrate that it is possible to involve undergraduates in publishable physical chemistry research;and to provide guidance on how to approach the challenges of physical chemistry research at a PUI. The material highlights the impactful training efforts within the undergraduate research environment which are essential for developing a pipeline of enthusiastic and capable talent heading to graduate schools or industrial and secondary education careers. This important work provides a "how to"by way of primary research examples involving various experimental and theoretical physical chemistry subfields. © 2022 American Chemical Society.

11.
Vaccine ; 2022.
Article in English | ScienceDirect | ID: covidwho-2159912

ABSTRACT

Background In early 2020, developing vaccines was an urgent need for preventing COVID-19 from a contingency perspective. Methods S-268019-a is a recombinant protein-based vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprising a modified recombinant spike protein antigen adjuvanted with agatolimod sodium, a Toll-like receptor-9 agonist. In the preclinical phase, it was administered intramuscularly twice at a 2-week interval in 7-week-old mice. Immunogenicity was assessed, and the mice were challenged intranasally with mouse-adapted SARS-CoV-2 at 2 and 8 weeks, respectively, after the second immunization. After confirming the preclinical effect, a Phase 1/2, randomized, parallel-group clinical study was conducted in healthy adults (aged 20-64 years). All participants received 2 intramuscular injections at various combinations of the antigen and the adjuvant (S-910823/agatolimod sodium, in μg: 12.5/250, 25/250, 50/250, 25/500, 50/500, 100/500, 10/500, 100/100, 200/1000) or placebo (saline) in an equivalent volume at a 3-week interval and were followed up until Day 50 in this interim analysis. Results In the preclinical studies, S-268019-a was safe and elicited robust immunoglobulin G (IgG) and neutralizing antibody responses in mice. When challenged with SARS-CoV-2, all S-268019-a-treated mice survived and maintained weight until 10 days, whereas all placebo- or adjuvant-treated (without antigen) mice died within 6 days. In the Phase 1/2 trial, although S-268019-a was well tolerated in adult participants, was safe up to Day 50, and elicited robust anti-spike protein IgG antibodies, it did not elicit sufficient neutralizing antibodies levels. Conclusions The S-268019-a vaccine was not sufficiently immunogenic in Japanese adults despite robust immunogenicity and efficacy in mice. Our results exemplify the innate challenges in translating preclinical data in animals to clinical trials, and highlight the need for continued research to overcome such barriers. (jRCT2051200092)

12.
Microbes and Infection ; : 105082, 2022.
Article in English | ScienceDirect | ID: covidwho-2159558

ABSTRACT

Available COVID-19 vaccine only provide protection for a limited time due in part to the rapid emergence of viral variants with spike protein mutations, necessitating the generation of new vaccines to combat SARS-CoV-2. Two serologically distinct replication-defective chimpanzee-origin adenovirus (Ad) vectors (AdC) called AdC6 and AdC7 expressing early SARS-CoV-2 isolate spike (S) or nucleocapsid (N) proteins, the latter expressed as a fusion protein within herpes simplex virus glycoprotein D (gD), were tested individually or as a mixture in a hamster COVID-19 SARS-CoV-2 challenge model. The S protein expressing AdC (AdC-S) vectors induced antibodies including those with neutralizing activity that in part cross-reacted with viral variants. Hamsters vaccinated with the AdC-S vectors were protected against serious disease and showed accelerated recovery upon SARS-CoV-2 challenge. Protection was enhanced if AdC-S vectors were given together with the AdC vaccines that expressed the gD N fusion protein (AdC-gDN). In contrast hamsters that just received the AdC-gDN vaccines showed only marginal lessening of symptoms compared to control animals. These results indicate that immune response to the N protein that is less variable than the S protein may potentiate and prolong protection achieved by the currently used S protein based genetic COVID-19 vaccines.

13.
European Polymer Journal ; : 111767, 2022.
Article in English | ScienceDirect | ID: covidwho-2158815

ABSTRACT

The global spread of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) has caused the loss of many human lives and severe economic losses. SARS-CoV-2 mediates its infection in humans via the spike glycoprotein. The receptor binding domain of the SARS-CoV-2 spike protein binds to its cognate receptor, angiotensin converting enzyme-2 (ACE2) to initiate viral entry. In this study, we examine how polymer modification of the spike protein receptor binding domain impacts binding to ACE2. The horseradish peroxidase conjugated receptor binding domain was modified with a range of polymers including hydrophilic N,N-dimethylacrylamide, hydrophobic N-isopropylacrylamide, cationic 3-(N,N-dimethylamino)propylacrylamide, and anionic 2-acrylamido-2-methylpropane sulfonic acid polymers. The effect of polymer chain length was observed using N,N-dimethylacrylamide polymers with degrees of polymerization of 5, 10 and 25. Polymer conjugation of the receptor binding domain significantly reduced the interaction with ACE2 protein, as determined by an enzyme-linked immunosorbent assay. Stability analysis showed that these conjugates remained highly stable even after seven days incubation at physiological temperature. Hence, this study provides a detailed view of the effect specific type of modification using a library of polymers with different functionalities in interrupting RBD-ACE2 interaction.

14.
European Journal of Internal Medicine ; 2022.
Article in English | ScienceDirect | ID: covidwho-2158759

ABSTRACT

Among the various comorbidities potentially worsening the clinical outcome in patients hospitalized for the acute respiratory syndrome coronavirus-2 (SARS-CoV-2), hypertension is one of the most prevalent. However, the basic mechanisms underlying the development of severe forms of coronavirus disease 2019 (COVID-19) among hypertensive patients remain undefined and the direct association of hypertension with outcome in COVID-19 is still a field of debate. Experimental and clinical data suggest that SARS-CoV-2 infection promotes a rise in blood pressure (BP) during the acute phase of infection. Acute increase in BP and high in-hospital BP variability may be tied with acute organ damage and a worse outcome in patients hospitalized for COVID-19. In this context, the failure of the counter-regulatory renin-angiotensin-system (RAS) axis is a potentially relevant mechanism involved in the raise in BP. It is well recognized that the efficient binding of the Spike (S) protein to angiotensin converting enzyme 2 (ACE2) receptors mediates the virus entry into cells. Internalization of ACE2, downregulation and malfunction predominantly due to viral occupation, dysregulates the protective RAS axis with increased generation and activity of angiotensin (Ang) II and reduced formation of Ang1,7. Thus, the imbalance between Ang II and Ang1–7 can directly contribute to excessively rise BP in the acute phase of SARS-CoV-2 infection. A similar mechanism has been postulated to explain the raise in BP following COVID-19 vaccination ("Spike Effect” similar to that observed during the infection of SARS-CoV-2). S proteins produced upon vaccination have the native-like mimicry of SARS-CoV-2 S protein's receptor binding functionality and prefusion structure and free-floating S proteins released by the destroyed cells previously targeted by vaccines may interact with ACE2 of other cells, thereby promoting ACE2 internalization and degradation, and loss of ACE2 activities.

15.
BMC Pharmacol Toxicol ; 23(1):91, 2022.
Article in English | PubMed | ID: covidwho-2153688

ABSTRACT

BACKGROUND: The coronavirus disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became an international pandemic and created a public health crisis. The binding of the viral Spike glycoprotein to the human cell receptor angiotensin-converting enzyme 2 (ACE2) initiates viral infection. The development of efficient treatments to combat coronavirus disease is considered essential. METHODS: An in silico approach was employed to design amino acid peptide inhibitor against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The designed inhibitor (SARS-CoV-2 PEP 49) consists of amino acids with the α1 helix and the β4 - β5 sheets of ACE2. The PEP-FOLD3 web tool was used to create the 3D structures of the peptide amino acids. Analyzing the interaction between ACE2 and the RBD of the Spike protein for three protein data bank entries (6M0J, 7C8D, and 7A95) indicated that the interacting amino acids were contained inside two regions of ACE2: the α1 helical protease domain (PD) and the β4 - β5 sheets. RESULTS: Molecular docking analysis of the designed inhibitor demonstrated that SARS-CoV-2 PEP 49 attaches directly to the ACE2 binding site of the Spike protein with a binding affinity greater than the ACE2, implying that the SARS-CoV-2 PEP 49 model may be useful as a potential RBD binding blocker.

16.
Science of The Total Environment ; 862:160700, 2023.
Article in English | ScienceDirect | ID: covidwho-2150569

ABSTRACT

In this work, we report an impedimetric system for the detection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein. The sensing platform is based on recombinant Spike protein (SCoV2-rS) immobilized on the phytic acid doped polyaniline films (PANI-PA). The affinity interaction between immobilized SCoV2-rS protein and antibodies in the physiological range of concentrations was registered by electrochemical impedance spectroscopy. Analytical parameters of the sensing platform were tuned by the variation of electropolymerization times during the synthesis of PANI-PA films. The lowest limit of detection and quantification were obtained for electropolymerization time of 20 min and equalled 8.00 ± 0.20 nM and 23.93 ± 0.60 nM with an equilibrium dissociation constant of 3 nM. The presented sensing system is label-free and suitable for the direct detection of antibodies against SARS-CoV-2 in real patient serum samples after coronavirus disease 2019 and/or vaccination.

18.
Journal of Virus Eradication ; : 100307, 2022.
Article in English | ScienceDirect | ID: covidwho-2150230

ABSTRACT

Because of rapid emergence and circulation of the SARS-CoV-2 variants, especially Omicron which shows increased transmissibility and resistant to antibodies, there is an urgent need to develop novel therapeutic drugs to treat COVID-19. In this study we developed an in vitro cellular model to explore the regulation of ACE2 expression and its correlation with ACE2-mediated viral entry. We examined ACE2 expression in a variety of human cell lines, some of which are commonly used to study SARS-CoV-2. Using the developed model, we identified a number of inhibitors which reduced ACE2 protein expression. The greatest reduction of ACE2 expression was observed when CK869, an inhibitor of actin-related protein 2/3 (ARP2/3) complex, was combined with 5-(N-ethyl-N-isopropyl)-Amiloride (EIPA), an inhibitor of sodium-hydrogen exchangers (NHEs), after treatment for 24 hours. Using pseudotyped lentivirus expressing SARS-CoV-2 full-length spike protein, we found that ACE2-dependent viral entry was inhibited in CK869 + EIPA-treated Calu-3 and MDA-MB-468 cells. This study provides an in vitro model that can be used for screening of novel therapeutic candidates that may be warranted for further pre-clinical and clinical studies on COVID-19 countermeasures.

19.
J Theor Biol ; : 111376, 2022.
Article in English | PubMed | ID: covidwho-2150216

ABSTRACT

SARS-CoV-2 (SARS2) regularly mutates resulting to variants of concern (VOC) which have higher virulence and transmissibility rates while concurrently evading available therapeutic strategies. This highlights the importance of amino acid mutations occurring in the SARS2 spike protein structure since it may affect virus biology. However, this was never fully elucidated. Here, network analysis was performed based on the COVID-19 genomic epidemiology network between December, 2019-July, 2021. Representative SARS2 VOC spike protein models were generated and quality checked, protein model superimposition was done, and common contact based on contact mapping was established. Throughout this study, we found that: (1) certain individual variant-specific amino acid mutations can affect the spike protein structural pattern;(2) certain individual variant-specific amino acid mutations had no affect on the spike protein structural pattern;and (3) certain combination of variant-specific amino acids are putatively epistatic mutations that can potentially influence the VOC spike protein structural pattern. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

20.
Biochemical and Biophysical Research Communications ; 2022.
Article in English | ScienceDirect | ID: covidwho-2149376

ABSTRACT

Several SARS-CoV-2 variants of interest (VOI) have emerged since this virus was first identified as the etiologic agent responsible for COVID-19. Some of these variants have demonstrated differences in both virulence and transmissibility, as well as in evasion of immune responses in hosts vaccinated against the original strain of SARS-CoV-2. There remains a lack of definitive evidence that identifies the genetic elements that are responsible for the differences in transmissibility among these variants. One factor affecting transmissibility is the initial binding of the surface spike protein (SP) of SARS-CoV-2 to human angiotensin converting enzyme-2 (hACE2), the widely accepted receptor for SP. This step in the viral replication process is mediated by the receptor binding domain (RBD) of SP that is located on the surface of the virus. This current study was conducted with the aim of assessing potential differences in binding affinity between recombinant hACE2 and the RBDs of emergent SARS-CoV-2 WHO VOIs. Mutations that affect the binding affinity of SP play a dominant initial role in the infectivity of the virus.

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