A comprehensive SARS-CoV-2 and COVID-19 review, Part 1: Intracellular overdrive for SARS-CoV-2 infection

doi:10.1038/s41431-022-01108-8

Review

. 2022 Aug;30(8):889-898.

doi: 10.1038/s41431-022-01108-8. Epub 2022 May 16.

A comprehensive SARS-CoV-2 and COVID-19 review, Part 1: Intracellular overdrive for SARS-CoV-2 infection

David A Jamison Jr^#¹, S Anand Narayanan^#^{2

3}, Nídia S Trovão^{1

4}, Joseph W Guarnieri^{1

5}, Michael J Topper^{1

6}, Pedro M Moraes-Vieira^{1

7

8

9}, Viktorija Zaksas^{1

10}, Keshav K Singh^{1

11}, Eve Syrkin Wurtele^{1

12}, Afshin Beheshti^{13

14

15}

Affiliations

¹ COVID-19 International Research Team, Medford, MA, USA.
² COVID-19 International Research Team, Medford, MA, USA. anarayan09@gmail.com.
³ Department of Nutrition & Integrative Physiology, Florida State University, Tallahassee, FL, USA. anarayan09@gmail.com.
⁴ Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
⁵ Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁶ Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
⁷ Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
⁸ Obesity and Comorbidities research Center (OCRC), University of Campinas, Campinas, SP, Brazil.
⁹ Experimental Medicine Research Cluster, University of Campinas, Campinas, Brazil.
¹⁰ Center for Translational Data Science, University of Chicago, Chicago, IL, USA.
¹¹ Department of Genetics, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
¹² Center for Metabolic Biology, Bioinformatics and Computational Biology, and Genetics Development, and Cell Biology, Iowa State University, Ames, IA, USA.
¹³ COVID-19 International Research Team, Medford, MA, USA. afshin.beheshti@nasa.gov.
¹⁴ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. afshin.beheshti@nasa.gov.
¹⁵ KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA, USA. afshin.beheshti@nasa.gov.

^# Contributed equally.

PMID: 35577935
PMCID: PMC9108708
DOI: 10.1038/s41431-022-01108-8

Review

A comprehensive SARS-CoV-2 and COVID-19 review, Part 1: Intracellular overdrive for SARS-CoV-2 infection

David A Jamison Jr et al. Eur J Hum Genet. 2022 Aug.

. 2022 Aug;30(8):889-898.

doi: 10.1038/s41431-022-01108-8. Epub 2022 May 16.

Authors

Affiliations

¹ COVID-19 International Research Team, Medford, MA, USA.
² COVID-19 International Research Team, Medford, MA, USA. anarayan09@gmail.com.
³ Department of Nutrition & Integrative Physiology, Florida State University, Tallahassee, FL, USA. anarayan09@gmail.com.
⁴ Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
⁵ Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁶ Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
⁷ Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
⁸ Obesity and Comorbidities research Center (OCRC), University of Campinas, Campinas, SP, Brazil.
⁹ Experimental Medicine Research Cluster, University of Campinas, Campinas, Brazil.
¹⁰ Center for Translational Data Science, University of Chicago, Chicago, IL, USA.
¹¹ Department of Genetics, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
¹² Center for Metabolic Biology, Bioinformatics and Computational Biology, and Genetics Development, and Cell Biology, Iowa State University, Ames, IA, USA.
¹³ COVID-19 International Research Team, Medford, MA, USA. afshin.beheshti@nasa.gov.
¹⁴ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. afshin.beheshti@nasa.gov.
¹⁵ KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA, USA. afshin.beheshti@nasa.gov.

^# Contributed equally.

PMID: 35577935
PMCID: PMC9108708
DOI: 10.1038/s41431-022-01108-8

Abstract

COVID-19, the disease caused by SARS-CoV-2, has claimed approximately 5 million lives and 257 million cases reported globally. This virus and disease have significantly affected people worldwide, whether directly and/or indirectly, with a virulent pathogen that continues to evolve as we race to learn how to prevent, control, or cure COVID-19. The focus of this review is on the SARS-CoV-2 virus' mechanism of infection and its proclivity at adapting and restructuring the intracellular environment to support viral replication. We highlight current knowledge and how scientific communities with expertize in viral, cellular, and clinical biology have contributed to increase our understanding of SARS-CoV-2, and how these findings may help explain the widely varied clinical observations of COVID-19 patients.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1. SARS-CoV-2 structure.**
Structural elements of the virus, including the spike protein, envelope, membrane, and internal components such as the viral single-stranded RNA and nucleocapsid proteins (above). SARS-CoV-2 genome components (below).

**Fig. 2. SARS-CoV-2 binding, intracellular internalization, and intracellular processes.**
Structural interactions between the virus and target cell, including the viral spike protein, ACE2-receptor, TMPRSS2 reaction to cleave and begin the viral intracellular internalization (above, A), and consequent signal transduction pathways stimulated by the virus as it hijacks pathways to turn the infected cell into a SARS-CoV-2 producing factory (below, B).

**Fig. 3. SARS-CoV-2 effects on Ca²⁺ signaling.**
Structural elements of the virus, including the spike protein, envelope, membrane, and internal components such as the viral single-stranded RNA and nucleocapsid proteins (above).

**Fig. 4. SARS-CoV-2 viral internalization & cellular hijacking.**
Metabolic pathways and shifts that lead to cellular dysregulation and viral activation to lead towards viral replication (above).

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References

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[1] Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020;20:533–4. - PMC - PubMed

[2] Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020;20:533–4. - PMC - PubMed

[3] Van Egeren D, Novokhodko A, Stoddard M, Tran U, Zetter B, Rogers M, et al. Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein. PloS One. 2021;16:e0250780. doi: 10.1371/journal.pone.0250780. - DOI - PMC - PubMed

[4] Van Egeren D, Novokhodko A, Stoddard M, Tran U, Zetter B, Rogers M, et al. Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein. PloS One. 2021;16:e0250780. doi: 10.1371/journal.pone.0250780. - DOI - PMC - PubMed

[5] Yao H, Song Y, Chen Y, Wu N, Xu J, Sun C, et al. Molecular architecture of the SARS-CoV-2 virus. Cell. 2020;183:730–8. doi: 10.1016/j.cell.2020.09.018. - DOI - PMC - PubMed

[6] Yao H, Song Y, Chen Y, Wu N, Xu J, Sun C, et al. Molecular architecture of the SARS-CoV-2 virus. Cell. 2020;183:730–8. doi: 10.1016/j.cell.2020.09.018. - DOI - PMC - PubMed

[7] Liu J, Xie W, Wang Y, Xiong Y, Chen S, Han J, et al. A comparative overview of COVID-19, MERS and SARS. Int J Surg. 2020;81:1–8. doi: 10.1016/j.ijsu.2020.07.032. - DOI - PMC - PubMed

[8] Liu J, Xie W, Wang Y, Xiong Y, Chen S, Han J, et al. A comparative overview of COVID-19, MERS and SARS. Int J Surg. 2020;81:1–8. doi: 10.1016/j.ijsu.2020.07.032. - DOI - PMC - PubMed

[9] Grifoni A, Sidney J, Zhang Y, Scheuermann RH, Peters B, Sette A. A sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARS-CoV-2. Cell Host Microbe. 2020;27:671–80. doi: 10.1016/j.chom.2020.03.002. - DOI - PMC - PubMed

[10] Grifoni A, Sidney J, Zhang Y, Scheuermann RH, Peters B, Sette A. A sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARS-CoV-2. Cell Host Microbe. 2020;27:671–80. doi: 10.1016/j.chom.2020.03.002. - DOI - PMC - PubMed

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A comprehensive SARS-CoV-2 and COVID-19 review, Part 1: Intracellular overdrive for SARS-CoV-2 infection

Affiliations

A comprehensive SARS-CoV-2 and COVID-19 review, Part 1: Intracellular overdrive for SARS-CoV-2 infection

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Affiliations

Abstract

Conflict of interest statement

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