Pre-exascale HPC approaches for molecular dynamics simulations. Covid-19 research: A use case.

Exascale computing has been a dream for ages and is close to becoming a reality that will impact how molecular simulations are being performed, as well as the quantity and quality of the information derived for them. We review how the biomolecular simulations field is anticipating these new architectures, making emphasis on recent work from groups in the BioExcel Center of Excellence for High Performance Computing. We exemplified the power of these simulation strategies with the work done by the HPC simulation community to fight Covid-19 pandemics. This article is categorized under:Data Science > Computer Algorithms and ProgrammingData Science > Databases and Expert SystemsMolecular and Statistical Mechanics > Molecular Dynamics and Monte-Carlo Methods.

Pre‐exascale HPC approaches for molecular dynamics simulations. Covid‐19 research: A use case

Exascale computing has been a dream for ages and is close to becoming a reality that will impact how molecular simulations are being performed, as well as the quantity and quality of the information derived for them. We review how the biomolecular simulations field is anticipating these new architectures, making emphasis on recent work from groups in the BioExcel Center of Excellence for High Performance Computing. We exemplified the power of these simulation strategies with the work done by the HPC simulation community to fight Covid‐19 pandemics. This article is categorized under: Data Science > Computer Algorithms and Programming Data Science > Databases and Expert Systems Molecular and Statistical Mechanics > Molecular Dynamics and Monte‐Carlo Methods From the onset of the COVID‐19 pandemic, the computational biology community has made a huge effort to consolidate resources and protocols, providing meaningful insights into the molecular aspects of the viral infection at an unprecedented pace. We review these latest developments across multiple scales ‐ from small‐molecule drug candidates to functionally important molecules to the whole viral particles ‐ as well as key advancements in the computational field that made them possible.

Mechanism of reaction of RNA-dependent RNA polymerase from SARS-CoV-2.

We combine molecular dynamics, statistical mechanics, and hybrid quantum mechanics/molecular mechanics simulations to describe mechanistically the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp). Our study analyzes the binding mode of both natural triphosphate substrates as well as remdesivir triphosphate (the active form of drug), which is bound preferentially over ATP by RdRp while being poorly recognized by human RNA polymerase II (RNA Pol II). A comparison of incorporation rates between natural and antiviral nucleotides shows that remdesivir is incorporated more slowly into the nascent RNA compared with ATP, leading to an RNA duplex that is structurally very similar to an unmodified one, arguing against the hypothesis that remdesivir is a competitive inhibitor of ATP. We characterize the entire mechanism of reaction, finding that viral RdRp is highly processive and displays a higher catalytic rate of incorporation than human RNA Pol II. Overall, our study provides the first detailed explanation of the replication mechanism of RdRp.

Cardiovascular Considerations for the Internist and Hospitalist in the COVID-19 Era.

It is clear that existing cardiovascular disease is a major risk factor for COVID-19 and related adverse outcomes. In addition to acute respiratory syndrome, a large cohort also develop myocardial or vascular dysfunction, in part from inflammation and renin angiotensin system activation with increased sympathetic outflow, cardiac arrhythmias, ischemia, heart failure, and thromboembolic complications that portend poor outcomes related to COVID-19. We summarize recent information for hospitalists and internists on the front line of this pandemic regarding its cardiovascular impacts and management and the need for cardiovascular consultation.

Severe COVID-19 After Recent Heart Transplantation Complicated by Allograft Dysfunction.

A 50-year-old male presented with atrial flutter 25 days after heart and kidney transplantation. Rejection was excluded, but he developed severe COVID-19 infection with cardiac allograft dysfunction. Despite continued corticosteroid and tacrolimus therapy, he remained aviremic. Respiratory and myocardial functions recovered after a week of mechanical ventilation. The cardiomyopathy was stress induced. (Level of Difficulty: Advanced.).