Levels of genetic diversity of SARS-CoV-2 virus: reducing speculations about the genetic variability of the virus in South America (preprint)

In this work, we evaluated the levels of genetic diversity in 38 complete Genomes of SARS-CoV-2 from six countries in South America, using specific methodologies for paired FST, AMOVA, mismatch, demographic and spatial expansions, molecular diversity and for the time of evolutionary divergence. The analyses showed non-significant evolutionary divergences within and between the six countries, as well as a significant similarity to the time of genetic evolutionary divergence between all populations. Thus, it seems safe to affirm that we will find similar results for the other Countries of South America, reducing speculation about the existence of rapid and silent mutations that, although there are as we have shown in this work, do not increase, until this moment, the genetic variability of the Virus, a fact that would hinder the work with molecular targets for vaccines and drugs in general.

SARS-CoV-2 ribosomal frameshifting pseudoknot: Improved secondary structure prediction and detection of inter-viral structural similarity (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the COVID-19 pandemic; a pandemic of a scale that has not been seen in the modern era. Despite over 29 million reported cases and over 900,000 deaths worldwide as of September 2020, herd immunity and widespread vaccination efforts by many experts are expected to be insufficient in addressing this crisis for the foreseeable future. Thus, there is an urgent need for treatments that can lessen the effects of SARS-CoV-2 in patients who become seriously affected. Many viruses including HIV, the common cold, SARS-CoV and SARS-CoV-2 use a unique mechanism known as -1 programmed ribosomal frameshifting (-1 PRF) to successfully replicate and infect cells in the human host. SARS-CoV (the coronavirus responsible for SARS) and SARS-CoV-2 possess a unique RNA structure, a three-stemmed pseudoknot, that stimulates -1 PRF. Recent experiments identified that small molecules can be introduced as antiviral agents to bind with the pseudoknot and disrupt its stimulation of -1 PRF. If successfully developed, small molecule therapy that targets -1 PRF in SARS-CoV-2 is an excellent strategy to improve patients' prognoses. Crucial to developing these successful therapies is modeling the structure of the SARS-CoV-2 -1 PRF pseudoknot. Following a structural alignment approach, we identify similarities in the -1 PRF pseudoknots of the novel coronavirus SARS-CoV-2, the original SARS-CoV, as well as a third coronavirus: MERS-CoV, the coronavirus responsible for Middle East Respiratory Syndrome (MERS). In addition, we provide a better understanding of the SARS-CoV-2 -1 PRF pseudoknot by comprehensively investigating the structural landscape using a hierarchical folding approach. Since understanding the impact of mutations is vital to long-term success of treatments that are based on predicted RNA functional structures, we provide insight on SARS-CoV-2 -1 PRF pseudoknot sequence mutations and their effect on the resulting structure and its function.

Emergence and expansion of highly infectious spike:D614G mutant SARS-CoV-2 in central India (preprint)

COVID 19 has emerged as global pandemic with largest damage to the economy and human psyche. The genomic signature deciphered during the ongoing pandemic period is valuable to understand the virus evolutionary patterns and spread across the globe. Increased availability of genome information of circulating strain in our country will enable to generate selective details in virulent and non virulent markers to prophylaxis and therapeutic interventions. The first case of SARS CoV-2 was detected in Chambal region of Madhya Pradesh state in mid of March 2020 followed by multiple introduction events and expansion of COVID-19 cases within 3 months in this region. We analyzed around 5000 COVID-19 suspected samples referred to Defence Research and Development Establishment, Gwalior, Madhya Pradesh. A total of 136 cases were found positive over a span of three months period this includes virus introduction to region and further spread. Whole genome sequences employing Oxford nanopore technology were deciphered for 26 SARS-CoV-2 circulating in 10 different districts in Madhya Pradesh State of India. The region witnessed index cases with multiple travel history responsible for introduction of COVID-19 followed by remarkable expansion of virus. The genome wide substitutions including in important viral proteins were observed. The detailed phylogenetic analysis revealed the circulating SARS-CoV-2 clustered in multiple clades A2a, A4 and B. The cluster wise segregation was observed suggesting multiple introduction links and evolution of virus in the region. This is the first comprehensive details of whole genome sequence analysis from central India region, which will add genome wide knowledge towards diagnostic and therapeutic interventions.