Dahlquist:COVID-19 Research Project

Lab Notebook

TMPRSS2 Lab Notebook

Literature

Collections

• LitCovid literature database
  • LitCovid is a curated literature hub for tracking up-to-date scientific information about the 2019 novel Coronavirus.
• Coronavirus articles from The Lancet
• Coronavirus: Research, Commentary, and News Collection from Science
  • Coronavirus News from Science
• NIH Coronavirus webpage
• Virological.org: A discussion forum for analysis and interpretation of virus molecular evolution and epidemiology.

Scientific Articles (newest to oldest)

• Jaimes, J. A., André, N. M., Chappie, J. S., Millet, J. K., & Whittaker, G. R. (2020). Phylogenetic analysis and structural modeling of SARS-CoV-2 spike protein reveals an evolutionary distinct and proteolytically-sensitive activation loop. Journal of molecular biology.
• Pruimboom, Leo. 2020. “Methylation Pathways and SARS-CoV-2 Lung Infiltration and Cell Membrane-Virus Fusion Are Both Subject to Epigenetics.” Frontiers in Cellular and Infection Microbiology 10. https://doi.org/10.3389/fcimb.2020.00290.
• Zheng, Haoyi, and J. Jane Cao. 2020. “Angiotensin-Converting Enzyme Gene Polymorphism and Severe Lung Injury in Patients with Coronavirus Disease 2019.” The American Journal of Pathology, July. https://doi.org/10.1016/j.ajpath.2020.07.009
• Gemmati, Donato, Barbara Bramanti, Maria Luisa Serino, Paola Secchiero, Giorgio Zauli, and Veronica Tisato. 2020. “COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-Chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males?” International Journal of Molecular Sciences 21 (10): 3474. https://doi.org/10.3390/ijms21103474
• Li, G., He, X., Zhang, L., Ran, Q., Wang, J., Xiong, A., ... & Chang, C. (2020). Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19. Journal of autoimmunity, 102463.
• Chlamydas, S., Papavassiliou, A. G., & Piperi, C. (2020). Epigenetic mechanisms regulating COVID-19 infection. Epigenetics, 1-8.
• Teichmann, S., Regev, A. The network effect: studying COVID-19 pathology with the Human Cell Atlas. Nat Rev Mol Cell Biol 21, 415–416 (2020). doi:10.1038/s41580-020-0267-3
• Sawalha, A. H., Zhao, M., Coit, P., & Lu, Q. (2020). Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients. Clinical Immunology, 108410.
• Pinto, B. G., Oliveira, A. E., Singh, Y., Jimenez, L., Gonçalves, A. N. A., Ogava, R. L., ... & Nakaya, H. I. (2020). ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. MedRxiv.
• Liu, Y., Yan, L. M., Wan, L., Xiang, T. X., Le, A., Liu, J. M., ... & Zhang, W. (2020). Viral dynamics in mild and severe cases of COVID-19. The Lancet Infectious Diseases 20,1. doi:10.1016/S1473-3099(20)30232-2
• Wan, Y., Shang, J., Graham, R., Baric, R. S., & Li, F. (2020). Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. Journal of Virology, 94(7). doi:10.1128/JVI.00127-20
• Andersen, K.G., Rambaut, A., Lipkin, W.I. et al. (2020). The proximal origin of SARS-CoV-2. Nature Medicine 26, 450-452. doi:10.1038/s41591-020-0820-9
• Yan, R., Zhang, Y., Li, Y., Xia, L., Guo, Y., & Zhou, Q. (2020). Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science. doi:10.1126/science.abb2762
• Zhang, T., Wu, Q., & Zhang, Z. (2020). Probable Pangolin Origin of 2019-nCoV Associated with Outbreak of COVID-19. Current Biology 30, 1346-1351. doi:10.1016/j.cub.2020.03.022
• Hunter, P. (2020). The spread of the COVID‐19 coronavirus. EMBO Rep (2020)e50334. doi:10.15252/embr.202050334
• Moriyama, M., Hugentobler, W. J., & Iwasaki, A. (2020). Seasonality of respiratory viral infections. Annual Review of Virology, 7,1 doi: 10.1146/annurev-virology-012420-022445
• Zhou, P., Yang, X., Wang, X. et al. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273. doi:10.1038/s41586-020-2012-7
• Xu, Y., Lou, Z., Liu, Y., Pang, H., Tien, P., Gao, G. F., & Rao, Z. (2004). Crystal structure of severe acute respiratory syndrome coronavirus spike protein fusion core. Journal of Biological Chemistry, 279(47), 49414-49419. doi:10.1074/jbc.M408782200
  • This is the structure from the first SARS virus.

Articles about ACE2 polymorphisms relating to severity of SARS-CoV-2 infections

• Pati, A., Mahto, H., Padhi, S., & Panda, A. K. (2020). ACE deletion allele is associated with susceptibility to SARS-CoV-2 infection and mortality rate: An epidemiological study in the Asian population. Clinica Chimica Acta.
• Ziegler, C. G., Allon, S. J., Nyquist, S. K., Mbano, I. M., Miao, V. N., Tzouanas, C. N., ... & Feldman, J. (2020). SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell.
  • This article also has information regarding TMPRSS2 as well as ACE2
• Yamamoto, N. et al. (2020). SARS-CoV-2 infections and COVID-19 mortalities strongly correlate with ACE1 I/D genotype. Gene, Volume 758, 144944, ISSN 0378-1119. doi:10.1016/j.gene.2020.144944.
• Budheswar Dehury , Vishakha Raina , Namrata Misra & Mrutyunjay Suar (2020): Effect of mutation on structure, function and dynamics of receptor binding domain of human SARS-CoV-2 with host cell receptor ACE2: a molecular dynamics simulations study, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2020.1802348
• Hussain, M, Jabeen, N, Raza, F, et al. Structural variations in human ACE2 may influence its binding with SARS‐CoV‐2 spike protein. J Med Virol. 2020; 92: 1580– 1586. doi:10.1002/jmv.25832
• Alireza Paniri, Mohammad Mahdi Hosseini & Haleh Akhavan-Niaki (2020) First comprehensive computational analysis of functional consequences of TMPRSS2 SNPs in susceptibility to SARS-CoV-2 among different populations, Journal of Biomolecular Structure and Dynamics, DOI: 10.1080/07391102.2020.1767690
  • Rather than studying ACE2, this article focuses on TMPRSS2, a protein that activates the virus.
• Devaux CA, Rolain JM, Raoult D. ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. J Microbiol Immunol Infect. 2020;53(3):425-435. doi:10.1016/j.jmii.2020.04.015
• Luke Wooster, Christopher J Nicholson, Haakon H Sigurslid, Christian L Lino Cardenas, Rajeev Malhotra. Polymorphisms in the ACE2 Locus Associate with Severity of COVID-19 Infection. medRxiv. doi:10.1101/2020.06.18.20135152
  • not peer-reviewed
• Matteo Calcagnile, Patricia Forgez, Antonio Iannelli, Cecilia Bucci, Marco Alifano, Pietro Alifano. ACE2 polymorphisms and individual susceptibility to SARS-CoV-2 infection: insights from an in silico study. bioRxiv. doi:10.1101/2020.04.23.057042
  • not peer-reviewed

Questions

1. Can mutations in the ACE I/II gene reveal susceptibility to severity of SARS-CoV-2 infection?
2. Are heightened levels of ACE2 expression in COVID-19 patients with pre-existing conditions a key factor in their increased disease severity?
3. What epigenetic modifications occur to ACE2 throughout COVID-19 pathology? Can they be altered?
4. How do epigenetic changes associated with aging result in higher expression of the ACE2 gene and thus lead to increased COVID-19 susceptibility?
5. What role does the expression of the ACE2 D allele play in increasing severe COVID-19 outcomes among particular populations?
6. Could mosaicism in XX females afford higher immunity to COVID-19 since the gene for ACE2 is carried on the X chromosome?
7. What role does the genetically distinct activation loop of the SARS-CoV-2 S protein have on its transmission and pathogenicity?
   • What implications do the differences have on S protein interaction with human ACE II?

Tracking Number of Cases

• Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU) (Global)
• Worldometers.info (Global)
• The COVID Tracking Project (USA)
• California Cases Tracked by the LA Times

News & Websites

• Straiton, J. (2020). Genetic variant puts African-American populations at greater risk of hydroxychloroquine cardiac complications - BioTechniques
• Matacic, C. (2020). Blood vessel attack could trigger coronavirus’ fatal ‘second phase’
• Lake, F. (2020). Coronavirus Vaccine Updates and Information, Biotechniques
• Garrett, L. (2020). COVID-19: the medium is the message. The Lancet, 385(10228),942-943. doi:10.1016/S0140-6736(20)30600-0
• Jenny Straiton and Caitlin Killen (2020). Coronavirus: sorting the fact from the fiction, Biotechniques
• Oldach, L. (2020). Anatomy of a molecule: What makes remdesivir unique? ASBMB
  • Remdesivir is a possible antiviral treatment for SARS-CoV-2.
• NIH news release about Remdesivir clinical trial
• Stevens, H. (2020). Why Outbreaks like Coronavirus Spread Exponentially and How to Flatten the Curve - Washington Post
• Gladstone Institutes COVID-19 page
• Kenji López-Alt, J. (2020). Food Safety and Coronavirus: A Comprehensive Guide. - Serious Eats

Testing

• Protocol for COVID-19 screening using CDC and WHO primers.
  • Version 1.0 (March 18, 2020), by Catie Anderson and Mark Zeller of the Scripps Research Institute
• Amanat et al., (2020). A serological assay to detect SARS-CoV-2 seroconversion in humans. MedRxiv. doi:10.1101/2020.03.17.20037713
• Clinical Studies of COVID-19
• Michael J. Loeffelholz & Yi-Wei Tang (2020) Laboratory Diagnosis of Emerging Human Coronavirus Infections — The State of the Art, Emerging Microbes & Infections, DOI: 10.1080/22221751.2020.1745095
• Commercial Test Kit from ThermoFisher
  • This is not an endorsement
• Bio-Rad SARS-CoV-2 / COVID-19 Assay and Research Solutions

Data

• COVID-19 Open Research Dataset (CORD-19)
• EMBL-EBI Pathogens page
  • This page includes a list of PDB records
• GISAID: Global Initiative on Sharing All Influenza Data
• PDB Coronavirus page
• UniProt release notes about SARS-CoV-2
• Virological.org Phylogenetic analysis of nCoV-2019 genomes 6 March 2020

NCBI

• SARS-CoV-2 sequencing from San Diego county
  • Andersen lab project page
• Genome record for Severe acute respiratory syndrome coronavirus 2, RefSeq ID NC_045512.2
• Reference Sequence: NC_045512.2 GenBank record
• List of reference genomes
• List of proteins
• List of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) Sequences
• Spike protein
• Taxonomy page

• Virus

Research Ethics

• Bauchner H, Golub RM, Zylke J. (2020). Editorial Concern—Possible Reporting of the Same Patients With COVID-19 in Different Reports. JAMA 323(13):1256. doi:10.1001/jama.2020.3980
• Lake F. (2020) COVID-19 Retractions Put the Spotlight on Bad Data, Biotechniques
• Jiang, S. (2020) Don’t rush to deploy COVID-19 vaccines and drugs without sufficient safety guarantees. Nature 579, 321. doi: 10.1038/d41586-020-00751-9

Teaching Resources

• Crowdsourced teaching resources from the American Society of Microbiology
• Sigma Xi COVID-19 Preparedness Kit
  • Has a series of links to science articles and other resources for social distancing/online learning
• Tech & Learning Free Online Learning Resources For Schools Affected by Coronavirus/COVID-19
• Crowdsourced COVID-19 teaching resources
• Johnathan Corum and Carl Zimmer (2020). How Coronavirus Hijacks Your Cells - NY Times
• Can blood from coronavirus survivors treat the newly ill?
• Coronaviruses 101: Focus on Molecular Virology Video
• The Science of Coronaviruses by 3D Molecular Designs
• COVID-19 resources from ISCB
• Foldit 1811: Coronavirus Binder Design: Round 3
• ISCB COVID-19 webinars