Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach
The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East re...
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| Published in | Biochimica et biophysica acta. Molecular basis of disease Vol. 1866; no. 10; p. 165878 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.10.2020
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| Subjects | |
| Online Access | Get full text |
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| Abstract | The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective.
Schematic representation of novel corona virus showing target proteins and its mechanism of host entry. [Display omitted]
•The recent exposure to SARS-CoV-2 has affected entire world, resulted >0.4 million deaths.•Potential drug targets of SARS-CoV-2 are highly conserved.•A slight structural difference makes available drugs ineffective against SARS-CoV-2.•Cytokine storm during SARS-CoV-2 infection may be targeted to handle COVID-19 patients.•Many FDA approved drugs are showing positive effects in clinical trials but further validation in large subject groups is required. |
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| AbstractList | The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective. The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective. Schematic representation of novel corona virus showing target proteins and its mechanism of host entry. [Display omitted] •The recent exposure to SARS-CoV-2 has affected entire world, resulted >0.4 million deaths.•Potential drug targets of SARS-CoV-2 are highly conserved.•A slight structural difference makes available drugs ineffective against SARS-CoV-2.•Cytokine storm during SARS-CoV-2 infection may be targeted to handle COVID-19 patients.•Many FDA approved drugs are showing positive effects in clinical trials but further validation in large subject groups is required. The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective. Schematic representation of novel corona virus showing target proteins and its mechanism of host entry. Unlabelled Image • The recent exposure to SARS-CoV-2 has affected entire world, resulted >0.4 million deaths. • Potential drug targets of SARS-CoV-2 are highly conserved. • A slight structural difference makes available drugs ineffective against SARS-CoV-2. • Cytokine storm during SARS-CoV-2 infection may be targeted to handle COVID-19 patients. • Many FDA approved drugs are showing positive effects in clinical trials but further validation in large subject groups is required. The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective.The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective. |
| ArticleNumber | 165878 |
| Author | Naqvi, Ahmad Abu Turab Hasan, Gulam Mustafa Singh, Indrakant K. Mohammad, Taj Fatima, Kisa Hariprasad, Gururao Fatima, Urooj Atif, Shaikh Muhammad Singh, Archana Hassan, Md. Imtaiyaz |
| Author_xml | – sequence: 1 givenname: Ahmad Abu Turab surname: Naqvi fullname: Naqvi, Ahmad Abu Turab organization: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India – sequence: 2 givenname: Kisa surname: Fatima fullname: Fatima, Kisa organization: Department of Biotechnology, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India – sequence: 3 givenname: Taj surname: Mohammad fullname: Mohammad, Taj organization: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India – sequence: 4 givenname: Urooj surname: Fatima fullname: Fatima, Urooj organization: Department of Botany, Aligarh Muslim University, Aligarh 202002, U.P., India – sequence: 5 givenname: Indrakant K. surname: Singh fullname: Singh, Indrakant K. organization: Department of Zoology, Deshbandhu College, University of Delhi, Kalkaji, New Delhi 110 019, India – sequence: 6 givenname: Archana surname: Singh fullname: Singh, Archana organization: Department of Botany, Hansraj College, University of Delhi, Delhi, 110007, India – sequence: 7 givenname: Shaikh Muhammad surname: Atif fullname: Atif, Shaikh Muhammad organization: Department of Medicine, University of Colorado, Aurora, CO, USA – sequence: 8 givenname: Gururao surname: Hariprasad fullname: Hariprasad, Gururao organization: Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India – sequence: 9 givenname: Gulam Mustafa surname: Hasan fullname: Hasan, Gulam Mustafa organization: Department of Biochemistry, College of Medicine, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia – sequence: 10 givenname: Md. Imtaiyaz surname: Hassan fullname: Hassan, Md. Imtaiyaz email: mihassan@jmi.ac.in organization: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32544429$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Betacoronavirus - genetics Betacoronavirus - isolation & purification Betacoronavirus - pathogenicity Comparative genomics Coronavirus Infections - drug therapy Coronavirus Infections - pathology Coronavirus Infections - virology COVID-19 Cytokines - metabolism Drug target Genetic Variation Genome, Viral Humans Middle East Respiratory Syndrome Coronavirus - genetics Middle East Respiratory Syndrome Coronavirus - isolation & purification Middle East Respiratory Syndrome Coronavirus - pathogenicity Molecular basis of pathogenesis Molecular evolution Pandemics Pneumonia, Viral - drug therapy Pneumonia, Viral - pathology Pneumonia, Viral - virology RNA-Dependent RNA Polymerase - genetics SARS-CoV-2 Spike Glycoprotein, Coronavirus - chemistry |
| Title | Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach |
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