Virtual Boot Camp: <scp>COVID</scp>‐19 evolution and structural biology

Burley, S.K.; Bromberg, Yana; Craig, P.; Duffy, Siobain; Dutta, Shuchismita; Hall, Bonnie L.; Hudson, Brian P.; Jiang, Jennifer; Khare, Sagar D.; Koeppe, Julia R.; Lubin, Joseph H.; Mills, Stephen A.; Pikaart, Michael J.; Roberts, Rebecca; Sarma, Vidur V.; Singh, Jitendra; Tischfield, Jay A.; Xie, Lingjun; Zardecki, Christine

doi:10.1002/bmb.21428

Cited by 6 publications

(6 citation statements)

References 6 publications

(5 reference statements)

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“…This work was initiated by research interns (undergraduates and one high school student) hosted virtually during the summer of 2020 by the Rutgers University Institute for Quantitative Biomedicine (IQB), the Rutgers University RISE Program, and the US‐funded RCSB Protein Data Bank headquartered at Rutgers 79–81 . Prior to the online five‐week research program, participating students and mentors received 1 week of online training in 3D molecular visualization and computational bioinformatics in the IQB “Summer of the Coronaverse” Online Boot Camp 82 . The methods used in the research study were developed, evaluated, and refined during the online Boot Camp.…”

Section: Methodsmentioning

confidence: 99%

Evolution of the SARS‐CoV‐2 proteome in three dimensions (3D) during the first 6 months of the COVID‐19 pandemic

et al. 2021

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Understanding the molecular evolution of the SARS‐CoV‐2 virus as it continues to spread in communities around the globe is important for mitigation and future pandemic preparedness. Three‐dimensional structures of SARS‐CoV‐2 proteins and those of other coronavirusess archived in the Protein Data Bank were used to analyze viral proteome evolution during the first 6 months of the COVID‐19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48 000 viral isolates revealed how each one of 29 viral proteins have undergone amino acid changes. Catalytic residues in active sites and binding residues in protein–protein interfaces showed modest, but significant, numbers of substitutions, highlighting the mutational robustness of the viral proteome. Energetics calculations showed that the impact of substitutions on the thermodynamic stability of the proteome follows a universal bi‐Gaussian distribution. Detailed results are presented for potential drug discovery targets and the four structural proteins that comprise the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and protein–protein and protein–nucleic acid interfaces. Characterizing the evolution of the virus in three dimensions provides testable insights into viral protein function and should aid in structure‐based drug discovery efforts as well as the prospective identification of amino acid substitutions with potential for drug resistance.

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Section: Methodsmentioning

confidence: 99%

Evolution of the SARS‐CoV‐2 proteome in three dimensions (3D) during the first 6 months of the COVID‐19 pandemic

et al. 2021

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“…These features allowed educators to facilitate active participation through real-time discussion, interactive tutorials, and student-led case and clinical topic presentations 11 ; Socratic questioning within virtual discussions of nursing care plans 12 ; collaborative case-based learning in biochemistry 13 ; and data analysis exercises during a virtual structural biology boot camp. 14 Another example of interactive videoconferencing is the University of New Mexico’s Project ECHO, which connects experts and health care providers in “all teach, all learn” telementoring sessions. These sessions, modeled on the grand rounds method of information sharing amongst clinicians, use case studies to promote discussion, disseminate knowledge, and offer support for participants.…”

Section: Transition To Online Learningmentioning

confidence: 99%

The Role of Technology in Health Professions Education During the COVID-19 Pandemic

et al. 2022

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The COVID-19 pandemic has sparked radical shifts in the ways that both health care and health professions education are delivered. Before the pandemic, some degree programs were offered fully online or in a hybrid format, but in-person learning was considered essential to the education and training of health professionals. Similarly, even as the use of telehealth was slowly expanding, most health care visits were conducted in-person. The need to maintain a safe physical distance during the pandemic rapidly increased the online provision of health care and health professions education, accelerating technology adoption in both academic and professional health care settings. Many health care professionals, educators, and patients have had to adapt to new communication modalities, often with little or no preparation. Before the pandemic, the need for cost-effective, robust methodologies to enable teaching across distances electronically was recognized. During the pandemic, online learning and simulation became essential and were often the only means available for continuity of education and clinical training. This paper reviews the transition to online health professions education and delivery during the COVID-19 pandemic and provides recommendations for moving forward.

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“…The proteases that liberate individual proteins from viral polyproteins after translation are significantly more conserved than the spike protein, particularly in their active sites. The main protease (MPro, nsp5) is responsible for peptide bond hydrolysis at 11 cleavage sites within the polyprotein 6 . Due to the relative stability of its active site and functional importance, SARS-CoV-2 MPro represents an attractive target for inhibitor discovery 7,8 .…”

Section: Introductionmentioning

confidence: 99%

A comprehensive survey of coronaviral main protease active site diversity in 3D: Identifying and analyzing drug discovery targets in search of broad specificity inhibitors for the next coronavirus pandemic

Lubin

Martinusen

Zardecki

et al. 2023

Preprint

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Although the rapid development of therapeutic responses to combat SARS-CoV-2 represents a great human achievement, it also demonstrates untapped potential for advanced pandemic preparedness. Cross-species efficacy against multiple human coronaviruses by the main protease (MPro) inhibitor nirmatrelvir raises the question of its breadth of inhibition and our preparedness against future coronaviral threats. Herein, we describe sequence and structural analyses of 346 unique MPro enzymes from all coronaviruses represented in the NCBI Virus database. Cognate substrates of these representative proteases were inferred from their polyprotein sequences. We clustered MPro sequences based on sequence identity and AlphaFold2-predicted structures, showing approximate correspondence with known viral subspecies. Predicted structures of five representative MPros bound to their inferred cognate substrates showed high conservation in protease:substrate interaction modes, with some notable differences. Yeast-based proteolysis assays of the five representatives were able to confirm activity of three on inferred cognate substrates, and demonstrated that of the three, only one was effectively inhibited by nirmatrelvir. Our findings suggest that comprehensive preparedness against future potential coronaviral threats will require continued inhibitor development. Our methods may be applied to candidate coronaviral MPro inhibitors to evaluate in advance the breadth of their inhibition and identify target coronaviruses potentially meriting advanced development of alternative countermeasures.

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Virtual Boot Camp: COVID‐19 evolution and structural biology

Cited by 6 publications

References 6 publications

Evolution of the SARS‐CoV‐2 proteome in three dimensions (3D) during the first 6 months of the COVID‐19 pandemic

Evolution of the SARS‐CoV‐2 proteome in three dimensions (3D) during the first 6 months of the COVID‐19 pandemic

The Role of Technology in Health Professions Education During the COVID-19 Pandemic

A comprehensive survey of coronaviral main protease active site diversity in 3D: Identifying and analyzing drug discovery targets in search of broad specificity inhibitors for the next coronavirus pandemic

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