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SARS-CoV-2 Mutations and COVID-19 Clinical Outcome: Mutation Global Frequency Dynamics and Structural Modulation Hold the Key.
Maurya, Ranjeet; Mishra, Pallavi; Swaminathan, Aparna; Ravi, Varsha; Saifi, Sheeba; Kanakan, Akshay; Mehta, Priyanka; Devi, Priti; Praveen, Shaista; Budhiraja, Sandeep; Tarai, Bansidhar; Sharma, Shimpa; Khyalappa, Rajesh J; Joshi, Meghnad G; Pandey, Rajesh.
  • Maurya R; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, India.
  • Mishra P; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
  • Swaminathan A; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, India.
  • Ravi V; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, India.
  • Saifi S; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, India.
  • Kanakan A; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, India.
  • Mehta P; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, India.
  • Devi P; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, India.
  • Praveen S; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, India.
  • Budhiraja S; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
  • Tarai B; INtegrative GENomics of HOst-PathogEn (INGEN-HOPE) Laboratory, Council of Scientific & Industrial Research (CSIR)-Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi, India.
  • Sharma S; Max Super Speciality Hospital (A Unit of Devki Devi Foundation), Max Healthcare, Delhi, India.
  • Khyalappa RJ; Max Super Speciality Hospital (A Unit of Devki Devi Foundation), Max Healthcare, Delhi, India.
  • Joshi MG; Dr. D. Y. Patil Medical College, Pune, India.
  • Pandey R; Dr. D. Y. Patil Medical College, Pune, India.
Front Cell Infect Microbiol ; 12: 868414, 2022.
Article in English | MEDLINE | ID: covidwho-1779936
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had an enormous burden on the healthcare system worldwide as a consequence of its new emerging variants of concern (VOCs) since late 2019. Elucidating viral genome characteristics and its influence on disease severity and clinical outcome has been one of the crucial aspects toward pandemic management. Genomic surveillance holds the key to identify the spectrum of mutations vis-à-vis disease outcome. Here, in our study, we performed a comprehensive analysis of the mutation distribution among the coronavirus disease 2019 (COVID-19) recovered and mortality patients. In addition to the clinical data analysis, the significant mutations within the two groups were analyzed for their global presence in an effort to understand the temporal dynamics of the mutations globally in comparison with our cohort. Interestingly, we found that all the mutations within the recovered patients showed significantly low global presence, indicating the possibility of regional pool of mutations and the absence of preferential selection by the virus during the course of the pandemic. In addition, we found the mutation S194L to have the most significant occurrence in the mortality group, suggesting its role toward a severe disease progression. Also, we discovered three mutations within the mortality patients with a high cohort and global distribution, which later became a part of variants of interest (VOIs)/VOCs, suggesting its significant role in enhancing viral characteristics. To understand the possible mechanism, we performed molecular dynamics (MD) simulations of nucleocapsid mutations, S194L and S194*, from the mortality and recovered patients, respectively, to examine its impacts on protein structure and stability. Importantly, we observed the mutation S194* within the recovered to be comparatively unstable, hence showing a low global frequency, as we observed. Thus, our study provides integrative insights about the clinical features, mutations significantly associated with the two different clinical outcomes, its global presence, and its possible effects at the structural level to understand the role of mutations in driving the COVID-19 pandemic.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Front Cell Infect Microbiol Year: 2022 Document Type: Article Affiliation country: Fcimb.2022.868414

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Front Cell Infect Microbiol Year: 2022 Document Type: Article Affiliation country: Fcimb.2022.868414