Possible transmission flow of SARS-CoV-2 based on ACE2 features

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.

Notable sequence homology of the ORF10 protein introspects the architecture of SARS-COV-2

The global public health is endangered due to COVID-19 pandemic, which is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Despite having similar pathology to MERS and SARS-CoV, the infection fatality rate of SARS-CoV-2 is likely lower than 1%. SARS-CoV-2 has been reported to be uniquely characterized by the accessory protein ORF10, which contains eleven cytotoxic T lymphocyte (CTL) epitopes of nine amino acids length each, across various human leukocyte antigen (HLA) subtypes. In this study, all missense mutations found in sequence databases were examined across twnety-two unique SARS-CoV-2 ORF10 variants that could possibly alter viral pathogenicity. Some of these mutations decrease the stability of ORF10, e.g. I4L and V6I were found in the MoRF region of ORF10 which may also possibly contribute to Intrinsic protein disorder. Furthermore, a physicochemical and structural comparative analysis was carried out on SARS-CoV-2 and Pangolin-CoV ORF10 proteins, which share 97.37% amino acid homology. The high degree of physicochemical and structural similarity of ORF10 proteins of SARS-CoV-2 and Pangolin-CoV open questions about the architecture of SARS-CoV-2 due to the disagreement of these two ORF10 proteins over their sub-structure (loop/coil region), solubility, antigenicity and change from the strand to coil at amino acid position 26, where tyrosine is present. Altogether, SARS-CoV-2 ORF10 is a promising pharmaceutical target and a protein which should be monitored for changes which correlate to change pathogenesis and clinical course of COVID-19 infection.

A unique view of SARS-CoV-2 through the lens of ORF8 protein

Immune evasion is one of the unique characteristics of COVID-19 attributed to the ORF8 protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This protein is involved in modulating the host adaptive immunity through downregulating MHC (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the interferon mediated antiviral response of the host. To understand the immune perspective of the host with respect to the ORF8 protein, a comprehensive study of the ORF8 protein as well as mutations possessed by it, is performed. Chemical and structural properties of ORF8 proteins from different hosts, that is human, bat and pangolin, suggests that the ORF8 of SARS-CoV-2 and Bat RaTG13-CoV are very much closer related than that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 (SARS-CoV-2) are grouped into four classes based on their predicted effects. Based on geolocations and timescale of collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were endorsed upon sequence similarity and amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of rapid evolving SARS-CoV-2 through the ORF8.

Pathogenetic Perspective of Missense Mutations of ORF3a Protein of SARS-CoV2

One of the most important proteins for COVID-19 pathogenesis in SARS-CoV2 is the ORF3a protein which is the largest accessory protein among others accessory proteins coded by coronavirus genome. The major roles of the protein include virulence, infectivity, ion channel activity, morphogenesis and virus release. The coronavirus, SARS-CoV2 is continuously evolving naturally and thereby the encoded proteins are also mutating rapidly. Therefore, critical study of mutations in ORF3a is certainty important from the pathogenetic perspective. Here, a sum of 175 various non-synonymous mutations in the ORF3a protein of SARS-CoV2 are identified and their corresponding effects in structural stability and functions of the protein ORF3a are studied. Broadly three different classes of mutations, such as neutral, disease and mixed (neutral and disease) type mutations were observed. Consecutive mutations in some ORF3a proteins are established based on timeline of detection of mutations. Considering the amino acid compositions over the ORF3a primary protein sequences, twenty clusters are detected based on K-means clustering method. Our findings on 175 novel mutations of ORF3a proteins will extend our knowledge of ORF3a, a vital accessory protein in SARS-CoV2, which would assist to enlighten on the pathogenicity of this life-threatening COVID-19.

Predictive Model with Analysis of the Initial Spread of COVID-19 in India

The Coronavirus Disease 2019 (COVID-19) has currently ravaged through the world, resulting in over three million confirmed cases and over two hundred thousand deaths, a complete change in daily life as we know it, worldwide lock-downs, travel restrictions, as well as heightened hygiene measures and physical distancing. Being able to analyse and predict the spread of this epidemic-causing disease is hence of utmost importance now, especially as it would help in the reasoning behind important decisions drastically affecting countries and their people, as well as in ensuring efficient resource and utility management. However, the needs of the people and specific conditions of the spread are varying widely from country to country. In this article, we have conducted an in-depth analysis of the spread of COVID-19 in India, patient statistics, as well as proposed a mathematical prediction system that has succeeded in predicting the following days number of cases with 83% accuracy, ever since the first COVID-19 case was declared in India.