Friday, June 5, 2020
SARS CoV-2/COVID-19 Literature Digest
For the Week Ending June 5, 2020
As scientists begin to learn more about the SARS-CoV2 virus and COVID-19 disease, a number of critical findings have been published. In this literature digest, we highlight some of the top SARS-CoV2/COVID-19 publications.

Special thanks to Chiara Evans, Jonathan Khan, Helen Hoxie, and Anthony Antonelli for their support in compiling this digest.
Basic Science Immunology


This commentary discusses potential mechanisms by which COVID-19 appears to affect children to a lesser degree than adults.

Fischer, Alain. "Resistance of children to Covid-19. How?." Mucosal Immunology (2020): 1-3.

This review comments on the potential role of dysregulated Type 1 Interferon responses in COVID-19.

Acharya, Dhiraj, GuanQun Liu, and Michaela U. Gack. "Dysregulation of type I interferon responses in COVID-19." Nature Reviews Immunology (2020): 1-2.

This article thoroughly reviews the epidemiology, evolution, and genetic factors that potentially influence SARS-CoV-2 infection and COVID-19 disease.

Sironi, Manuela, et al. "SARS-CoV-2 and COVID-19: A genetic, epidemiological, and evolutionary perspective." Infection, Genetics and Evolution (2020): 104384.
Basic Science Drug Design

 
This study reports for the first time inhibitors found using an in-silico screen that could target the spike-binding domain to GRP78 which mediates the secondary entry of the virus. Additionally, it is also one of the few studies that have identified inhibitors against nsp15 – a non-structural protein essential for evading host immunity. Molecular dynamics simulation and subsequent total free energy calculation revealed that the complexes formed between the top-ranked ligands and their respective protein targets are dynamically stable with high total free energy of binding. Authors also include ADMET in-silico studies to support further investigation of these compounds.
 
Quimque, Mark Tristan J., et al. "Virtual Screening-Driven Drug Discovery of SARS-CoV2 Enzyme Inhibitors Targeting Viral Attachment, Replication, Post-Translational Modification and Host Immunity Evasion Infection Mechanisms." Journal of Biomolecular Structure and Dynamics just-accepted (2020): 1-23.

This study implemented an original virtual screening protocol for repositioning approved drugs in order to predict which of them could inhibit the main protease of the virus (M-pro), a key target for antiviral drugs given its essential role in the virus’ replication. This took advantage of the three sampling algorithms to generate hypothetic binding modes without relying on a single scoring function to rank the results. Seven possible SARS-CoV-2 M-pro inhibitors were predicted using this approach. Two have been selected by the COVID Moonshot initiative for in vitro testing. 

Gimeno, Aleix, et al. "Prediction of Novel Inhibitors of the Main Protease (M-pro) of SARS-CoV-2 through Consensus Docking and Drug Reposition." International Journal of Molecular Sciences 21.11 (2020): 3793.
Public Health


Sims and Kasprzyk-Hordern note that current methods of infectious disease passive surveillance are limited by underreporting. Wastewater Based Epidemiology offers a complementary measure of tracking, though perhaps in the case of COVID-19 may be a lagging indicator. Quilliam, et al. suggests that risks of COVID-19 transmission via a fecal-oral route ought to be understood as soon as possible to implement public health responses early and effectively during new outbreaks. Prior research has found COVID-19 detectable in sewage for up to 14 days, and thus wastewater surveillance could provide a non-invasive, pooled tool for widespread testing across towns and cities.

Sims, Natalie, and Barbara Kasprzyk-Hordern. "Future perspectives of wastewater-based epidemiology: monitoring infectious disease spread and resistance to the community level." Environment international (2020): 105689.

Authors looked at March 2020 admissions to two NewYork-Presbyterian hospitals in northern Manhattan and the outcomes by April 28, 2020. Median age was 62 years, 67% male, 82% with at least one chronic illness (most commonly hypertension and diabetes).

Cummings, Matthew J., et al. "Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study." The Lancet (2020).