Questioning the early events leading to the COVID-19 pandemic

Sixteen months after the January 30, 2020 declaration by the World Health Organization of a Public Health Emergency of International Concern regarding the spread of COVID-19, SARS-CoV-2 had infected ~ 170 million humans worldwide of which > 3.5 million had died. We critically examine information on the virus origin, when and where the first human cases occurred, and point to differences between Chinese and later clinical presentations. The official patient Zero was hospitalized in Wuhan, Hubei province, China, on December 8, 2019, but retrospective analyses demonstrate prior viral circulation. Coronaviruses are present in mammals and birds, but whether a wild animal (e.g. bat, pangolin) was the source of the human pandemic remains disputed. We present two contamination models, the spillover versus the circulation model; the latter brings some interesting hypotheses about previous SARS-CoV-2 virus circulation in the human population. The age distribution of hospitalized COVID-19 patients at the start of the epidemic differed between China and the USA–EU; Chinese hospitalized patients were notably younger. The first Chinese publications did not describe anosmia-dysgeusia, a cardinal symptom of COVID-19 in Europe and USA. The prominent endothelial involvement linked with thrombotic complications was discovered later. These clinical discrepancies might suggest an evolution of the virus.

In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin

The devastating impact of the COVID-19 pandemic caused by SARS–coronavirus 2 (SARS-CoV-2) has raised important questions about its origins and the mechanism of its transfer to humans. A further question was whether companion or commercial animals could act as SARS-CoV-2 vectors, with early data suggesting susceptibility is species specific. To better understand SARS-CoV-2 species susceptibility, we undertook an in silico structural homology modelling, protein–protein docking, and molecular dynamics simulation study of SARS-CoV-2 spike protein’s ability to bind angiotensin converting enzyme 2 (ACE2) from relevant species. Spike protein exhibited the highest binding to human (h)ACE2 of all the species tested, forming the highest number of hydrogen bonds with hACE2. Interestingly, pangolin ACE2 showed the next highest binding affinity despite having a relatively low sequence homology, whereas the affinity of monkey ACE2 was much lower despite its high sequence similarity to hACE2. These differences highlight the power of a structural versus a sequence-based approach to cross-species analyses. ACE2 species in the upper half of the predicted affinity range (monkey, hamster, dog, ferret, cat) have been shown to be permissive to SARS-CoV-2 infection, supporting a correlation between binding affinity and infection susceptibility. These findings show that the earliest known SARS-CoV-2 isolates were surprisingly well adapted to bind strongly to human ACE2, helping explain its efficient human to human respiratory transmission. This study highlights how in silico structural modelling methods can be used to rapidly generate information on novel viruses to help predict their behaviour and aid in countermeasure development.

Replication-Dependent Biogenesis of Turnip Crinkle Virus Long Noncoding RNAs

Long noncoding RNAs (lncRNAs) of virus origin accumulate in cells infected by many positive strand (+) RNA viruses to bolster viral infectivity. Their biogenesis mostly utilizes exoribonucleases of host cells that degrade viral genomic or subgenomic RNAs in the 5’-to-3’ direction until being stalled by well-defined RNA structures. Here we report a viral lncRNA that is produced by a novel replication-dependent mechanism. This lncRNA corresponds to the last 283 nucleotides of the turnip crinkle virus (TCV) genome, hence is designated tiny TCV subgenomic RNA (ttsgR). ttsgR accumulated to high levels in TCV-infected Nicotiana benthamiana cells when the TCV-encoded RNA-dependent RNA polymerase (RdRp), also known as p88, was overexpressed. Both (+) and (-) strand forms of ttsgR were produced in these cells in a manner dependent on the RdRp functionality. Strikingly, templates as short as ttsgR itself were sufficient to program ttsgR amplification, as long as the TCV-encoded replication proteins, p28 and p88, were provided in trans. Consistent with its replicational origin, ttsgR accumulation required a 5’ terminal G3(A/U)4 motif shown by others to be crucial for the replication of a TCV satellite RNA. More importantly, introducing a new G3(A/U)4 motif elsewhere in the TCV genome was alone sufficient to cause the emergence of another lncRNA. Collectively our results unveil a replication-dependent mechanism for the biogenesis of viral lncRNAs, thus suggesting that multiple mechanisms, individually or in combination, may be responsible for viral lncRNA production.

Identity and Similarity Percentages of SARS-CoV-2 Proteins Can Be Used as Indicators of the Virus Origin

There are three types of proteins in the coronaviruses; nonstructural, structural and accessory proteins. The coronaviruses proteins are essential for the viral replication and for the binding, invasion and regulation of the host cells metabolism and immunity. This article investigated the amino acid sequence similarity and identity percentages of 10 proteins present in SARS-CoV-2, SARS-CoV and the Rhinolophus affinis bat coronavirus (BatCoV RaTG13). The investigated proteins were 1ab polyprotein, spike protein, orf3a, envelope protein, membrane protein, orf6, orf7a, orf7b, orf8, and ncleocapsid protein. The online sequence alignment service of The European Molecular Biology Open Software Suite (EMBOSS) was used to determine the similarity and identity percentages of the three viruses proteins. The results showed that the similarity and identity percentages of the SARS-CoV-2 and BatCoV RaTG13 proteins are above 95% while the identity and similarity percentages of the SARS-CoV-2 and SARS-CoV are above 38%. The proteins of the SARS-CoV-2 and the BatCoV RaTG13 are of high identity and similarity percentages compared to those of the SARS-CoV-2 and the SARS-CoV.

Review of top five financial markets during the pandemic times

The purpose of this paper is to jot down the devastating impacts of COVID-19 towards the top five financial markets of the world and to see how they reacted back in different phases of COVID-19 from start till July 2020. The review is based on the financial market news, blogs, the governmental, and other financial bodies’ websites. The effects of the pandemic are like the damage never seen before in a much shorter time, vanishing a quarter portion of wealth in about a month and creating continuous uncertainties for investors throughout. China despite being the virus origin still performed well and better among all top markets whereas the rest all the stock exchanges remained inconsistent. This paper is the first of its kind to review the COVID-19 effects on the top five global stock markets and the governmental responses towards them. The study along with contributing to the existing literature is also assisting investors, analysts, specialists, and authorities to analyze their opinions w.r.t. stock markets performances, government responses, and their future market-related decisions.