ABSTRACT
One of the main obstacles in prevention and treatment of COVID-19 is the rapid evolution of the SARS-CoV-2 Spike protein. Given that Spike is the main target of common treatments of COVID-19, mutations occurring at this virulent factor can affect the effectiveness of treatments. The B.1.617.2 lineage of SARS-CoV-2, being characterized by many Spike mutations inside and outside of its receptor-binding domain (RBD), shows high infectivity and relative resistance to existing cures. Here, utilizing a wide range of computational biology approaches, such as immunoinformatics, molecular dynamics (MD), analysis of intrinsically disordered regions (IDRs), protein-protein interaction analyses, residue scanning, and free energy calculations, we examine the structural and biological attributes of the B.1.617.2 Spike protein. Furthermore, the antibody design protocol of Rosetta was implemented for evaluation the stability and affinity improvement of the Bamlanivimab (LY-CoV55) antibody, which is not capable of interactions with the B.1.617.2 Spike. We observed that the detected mutations in the Spike of the B1.617.2 variant of concern can cause extensive structural changes compatible with the described variation in immunogenicity, secondary and tertiary structure, oligomerization potency, Furin cleavability, and drug targetability. Compared to the Spike of Wuhan lineage, the B.1.617.2 Spike is more stable and binds to the Angiotensin-converting enzyme 2 (ACE2) with higher affinity.
ABSTRACT
Introduction: This study aimed to estimate the prevalence of dysphonia in patients with COVID-19. Materials and Methods: English and Persian studies that reported dysphonia in patients with COVID-19 were included. Review and case report studies were excluded. We searched Web of Science, PubMed, Google Scholar, and Scopus from January 1, 2020, to July 15, 2021. The prevalence of dysphonia was obtained by combining the results and weighing the sample sizes in the corresponding studies. Heterogeneity was evaluated using the Cochran Q test and I2Results: Of the 1830 articles identified, 7 studies (n=1410 patients) were included in the meta-analysis. The pooled prevalence of dysphonia was 31% (%95CI: 13%-48%). The prevalence rates of dysphonia in men and women with COVID-19 were 28.2% (%95CI: 14%-46%) and 32.8% (%95CI: 22%-45%), respectively.Conclusion: Because of the design of the included studies, the reliability of the results is limited. There was notable heterogeneity in the data, not because of publication bias, but rather the small sample sizes or the heterogeneity of the COVID-19 disease. About one-third of patients with COVID-19 may have dysphonia as the only symptom. Therefore, one should even be careful in approaching those who have only dysphonia. [ FROM AUTHOR] Copyright of Modern Rehabilitation is the property of Tehran University of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a large number of mutations in its genome have been reported. Some of the mutations occur in noncoding regions without affecting the pathobiology of the virus, while mutations in coding regions are significant. One of the regions where a mutation can occur, affecting the function of the virus is at the receptor-binding domain (RBD) of the spike protein. RBD interacts with angiotensin-converting enzyme 2 (ACE2) and facilitates the entry of the virus into the host cells. There is a lot of focus on RBD mutations, especially the displacement of N501Y which is observed in the UK/Kent, South Africa, and Brazilian lineages of SARS-CoV-2. Our group utilizes computational biology approaches such as immunoinformatics, protein-protein interaction analysis, molecular dynamics, free energy computation, and tertiary structure analysis to disclose the consequences of N501Y mutation at the molecular level. Surprisingly, we discovered that this mutation reduces the immunogenicity of the spike protein; also, displacement of Asn with Tyr reduces protein compactness and significantly increases the stability of the spike protein and its affinity to ACE2. Moreover, following the N501Y mutation secondary structure and folding of the spike protein changed dramatically.