Comprehensive analysis of genomic diversity of SARS-CoV-2 in different geographic regions of India: An endeavour to classify Indian SARS-CoV-2 strains on the basis of co-existing mutations
Abstract:Accumulation of mutations within the genome is the primary driving force for viral evolution within an endemic setting. This inherent feature often leads to altered virulence, infectivity and transmissibility as well as antigenic shift to escape host immunity, which might compromise the efficacy of vaccines and antiviral drugs. Therefore, we aimed at genome-wide analyses of circulating SARS-CoV-2 viruses for the emergence of novel co-existing mutations and trace their spatial distribution within India. Compreh… Show more
“…across Indian states and union territories compared over the three time terms. We observed a large number of non-clade defining mutations to co-occur within SARS-CoV2 strains from the states and union territories during the 'Term2' and 'Term3' which is consistent with earlier reports based on the sequences collected mostly in 'Term1' period (17). Consequently, a larger number of unique combinations among these cooccurred mutations were appeared during the latter half of the year 2020.…”
Section: Association Of Specific Mutations and Co-mutations With Patient Statussupporting
confidence: 90%
“…Several thousands of whole-genome sequences of the SARS-CoV2 from various parts of the country have been sequenced and subsequently deposited in global databases such as GISAID (16). Multiple works from India have highlighted the genomic diversity and the phylogenetic profiles of the prevalent strains in the country (7,17). However, more than 75% of the SARS-CoV2 sequences (2521 out of 3277 complete genomes from India) were deposited in the latter half of the year 2020.…”
Emergence of distinct viral clades has been observed in SARS-CoV2 variants across the world and India. Identification of the genomic diversity and the phylodynamic profiles of the prevalent strains of the country are critical to understand the evolution and spread of the variants. We performed whole-genome sequencing of 54 SARS-CoV2 strains collected from COVID-19 patients in Kolkata, West Bengal during August to October 2020. Phylogeographic and phylodynamic analyses were performed using these 54 and other sequences from India and abroad available in GISAID database. Spatio-temporal evolutionary dynamics of the pathogen across various regions and states of India over three different time periods in the year 2020 were analyzed. We estimated the clade dynamics of the Indian strains and compared the clade specific mutations and the co-mutation patterns across states and union territories of India over the time course. We observed that GR, GH and G (GISAID) or 20B and 20A (Nextstrain) clades were the prevalent clades in India during middle and later half of the year 2020. However, frequent mutations and co-mutations observed within the major clades across time periods do not show much overlap, indicating emergence of newer mutations in the viral population prevailing in the country. Further, we explored the possible association of specific mutations and co-mutations with the infection outcomes manifested within the Indian patients.
“…across Indian states and union territories compared over the three time terms. We observed a large number of non-clade defining mutations to co-occur within SARS-CoV2 strains from the states and union territories during the 'Term2' and 'Term3' which is consistent with earlier reports based on the sequences collected mostly in 'Term1' period (17). Consequently, a larger number of unique combinations among these cooccurred mutations were appeared during the latter half of the year 2020.…”
Section: Association Of Specific Mutations and Co-mutations With Patient Statussupporting
confidence: 90%
“…Several thousands of whole-genome sequences of the SARS-CoV2 from various parts of the country have been sequenced and subsequently deposited in global databases such as GISAID (16). Multiple works from India have highlighted the genomic diversity and the phylogenetic profiles of the prevalent strains in the country (7,17). However, more than 75% of the SARS-CoV2 sequences (2521 out of 3277 complete genomes from India) were deposited in the latter half of the year 2020.…”
Emergence of distinct viral clades has been observed in SARS-CoV2 variants across the world and India. Identification of the genomic diversity and the phylodynamic profiles of the prevalent strains of the country are critical to understand the evolution and spread of the variants. We performed whole-genome sequencing of 54 SARS-CoV2 strains collected from COVID-19 patients in Kolkata, West Bengal during August to October 2020. Phylogeographic and phylodynamic analyses were performed using these 54 and other sequences from India and abroad available in GISAID database. Spatio-temporal evolutionary dynamics of the pathogen across various regions and states of India over three different time periods in the year 2020 were analyzed. We estimated the clade dynamics of the Indian strains and compared the clade specific mutations and the co-mutation patterns across states and union territories of India over the time course. We observed that GR, GH and G (GISAID) or 20B and 20A (Nextstrain) clades were the prevalent clades in India during middle and later half of the year 2020. However, frequent mutations and co-mutations observed within the major clades across time periods do not show much overlap, indicating emergence of newer mutations in the viral population prevailing in the country. Further, we explored the possible association of specific mutations and co-mutations with the infection outcomes manifested within the Indian patients.
“…The acquisitive features usually lead to severe infectivity, altered virulence and better transmissibility besides antigenic shifting which facilitates host immunity escape. This also might compromise the vaccines efficacy and antiviral drugs ( Sadat et al, 2021 ; Sarkar et al, 2021 ).…”
The world has gone through the critical phase of SARS-CoV-2 crisis caused by the new variants of the virus. The globally concerted effort to characterize viral genomic mutations across different clades has revealed several changes in the coding and also non-coding regions which might lead to a violent presentation or re-infection occurrence.
Here, we studied a COVID-19 subject who represented the symptoms following the full recovery of the first infection. COVID-19 specific IgM and IgG were evaluated in both steps. The viral samples from oropharyngeal/nasopharyngeal were subjected to RT-PCR and full sequencing was done in both incidences. The sequencing data was fully investigated with the reference sequence of SARS-CoV-2 and the changes were detected.
The obtained data is in favor of re-infection with 128 days of interval. SARS-CoV-2 presented more severely in the second episode of the disease and the specific antibodies against COVID-19 were not detectable. Both infections were caused by the same clade 20G, however, the mutation rates were higher in the second incidence including 10 nucleotide substitutions which had rarely been reported before. In the present study, the nucleotide mutations in various regions of the viral genome have been presented. The re-infection could have significant effect on clinical implications as well as vaccination.
“…The ACE2 protein belongs to the membrane-bound carboxypeptidase family and is responsible for converting angiotensin II to angiotensin [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. It is widely distributed throughout the human body, with supramaximal levels in the small intestine, testis, kidneys, heart, thyroid, adipose tissue, colon, liver, bladder, adrenal glands and lungs (mainly in type II alveolar cells) and macrophages.…”
Section: Coronavirus: Concepts; Types; Compositions; Mechanisms Of Infection and Replicationmentioning
confidence: 99%
“…Finally, only in December 2020, the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom and the Food and Drug Administration (FDA) in the United States of America (USA) authorized the emergency use of Pfizer/BioNTech’s and Moderna’s vaccines against COVID-19 [ 5 ]. Nevertheless, worldwide vaccine plans are yet to be implemented and novel mutations of the SARS-CoV-2 are rapidly emerging [ 6 , 7 ] demanding continuous research on therapeutics to manage COVID-19. By the end of February 2021, the number of global deaths related to COVID-19 was close to 2.5 million.…”
The family of coronaviruses (CoVs) uses the autophagy machinery of host cells to promote their growth and replication; thus, this process stands out as a potential target to combat COVID-19. Considering the different roles of autophagy during viral infection, including SARS-CoV-2 infection, in this review, we discuss several clinically used drugs that have effects at different stages of autophagy. Among them, we mention (1) lysosomotropic agents, which can prevent CoVs infection by alkalinizing the acid pH in the endolysosomal system, such as chloroquine and hydroxychloroquine, azithromycin, artemisinins, two-pore channel modulators and imatinib; (2) protease inhibitors that can inhibit the proteolytic cleavage of the spike CoVs protein, which is necessary for viral entry into host cells, such as camostat mesylate, lopinavir, umifenovir and teicoplanin and (3) modulators of PI3K/AKT/mTOR signaling pathways, such as rapamycin, heparin, glucocorticoids, angiotensin-converting enzyme inhibitors (IECAs) and cannabidiol. Thus, this review aims to highlight and discuss autophagy-related drugs for COVID-19, from in vitro to in vivo studies. We identified specific compounds that may modulate autophagy and exhibit antiviral properties. We hope that research initiatives and efforts will identify novel or “off-label” drugs that can be used to effectively treat patients infected with SARS-CoV-2, reducing the risk of mortality.
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