SARS-CoV-2 is a new human coronavirus (CoV), which emerged in China in late 2019 and is responsible for the global COVID-19 pandemic that caused more than 59 million infections and 1.4 million deaths in 11 months. Understanding the origin of this virus is an important issue and it is necessary to determine the mechanisms of its dissemination in order to contain future epidemics. Based on phylogenetic inferences, sequence analysis and structure-function relationships of coronavirus proteins, informed by the knowledge currently available on the virus, we discuss the different scenarios evoked to account for the origin - natural or synthetic - of the virus. The data currently available is not sufficient to firmly assert whether SARS-CoV2 results from a zoonotic emergence or from an accidental escape of a laboratory strain. This question needs to be solved because it has important consequences on the evaluation of risk/benefit balance of our interaction with ecosystems, the intensive breeding of wild and domestic animals, as well as some lab practices and on scientific policy and biosafety regulations. Regardless of its origin, studying the evolution of the molecular mechanisms involved in the emergence of pandemic viruses is essential to develop therapeutic and vaccine strategies and to prevent future zoonoses. This article is a translation and update of a French article published in M{é}decine/Sciences, Aug/Sept 2020 (http://doi.org/10.1051/medsci/2020123).
Relevance: Laboratory diagnosis of the novel coronavirus (SARS-CoV-2) infection combined with quarantine for contacts of infected individuals affects the spread of SARS-CoV-2 infection and levels of related mortality. Practices for testing for SARS-CoV-2 infection vary geographically in Russia. For example, in the city of St. Petersburg, where mortality rate for COVID-19 is the highest in the Russian Federation on Oct. 25, 2020, every death for COVID-19 corresponds to 15.7 detected cases of COVID-19 in the population, while the corresponding number for the whole of Russia is 58.1, suggesting l…
We comparatively analyzed the spatiotemporal fluctuations of the 2019-novel coronavirus (COVID-19) and SARS outbreaks to understand their epidemiological characteristics. Methodologically, we introduced TPL (Taylor power law) to characterize their spatiotemporal heterogeneity/stability and Hubbell (2001) unified neutral theory of biodiversity (UNTB) [specifically Harris et al. (2015) HDP-MSN model (hierarchical Dirichlet process multi-site neutral model)] to approximate the metapopulation of coronavirus infections. First, TPL analysis suggested that the coronaviruses appear to have a specific …
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current global COVID-19 pandemic, in which millions of lives have been lost. Understanding the zoonotic evolution of the coronavirus may provide insights for developing effective vaccines, monitoring the transmission trends, and preventing new zoonotic infections. Homopolymeric nucleotide repeats (HP), the most simple tandem repeats, are a ubiquitous feature of eukaryotic genomes. Yet the HP distributions and roles in coronavirus genome evolution are poorly investigated. In this study, we characterize th…
Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. We introduce mutation ratio and mutation $h$-index to characterize the protein conservativen…
The transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of paramount importance to the controlling and combating of coronavirus disease 2019 (COVID-19) pandemic. Currently, near 15,000 SARS-CoV-2 single mutations have been recorded, having a great ramification to the development of diagnostics, vaccines, antibody therapies, and drugs. However, little is known about SARS-CoV-2 evolutionary characteristics and general trend. In this work, we present a comprehensive genotyping analysis of existing SARS-CoV-2 mutations. We reveal that host immune response…
Understanding the behaviour of hosts of SARS-CoV-2 is crucial to our understanding of the virus. A comparison of environmental features related to the incidence of SARS-CoV-2 with those of its potential hosts is critical. We examine the distribution of coronaviruses among bats. We analyse the distribution of SARS-CoV-2 in a nine-week period following lockdown in Italy, Spain, and Australia. We correlate its incidence with environmental variables particularly ultraviolet radiation, temperature, and humidity. We establish a clear negative relationship between COVID-19 and ultraviolet radiation, …
The COVID-19 pandemic has been a great catastrophe that upended human lives and caused millions of deaths all over the world. The rapid spread of the virus, with its early-stage exponential growth and subsequent 'waves', caught many medical professionals and decision-makers unprepared. Even though epidemiological models have been known for almost a century (since the 'Spanish Influenza' pandemic of 1918-20), the real-life spread of the SARS-CoV-2 virus often confounded the modelers. While the general framework of epidemiological models like SEIR (susceptible-exposed-infected-recovered) or SIR …
After the detection of coronavirus disease 2019 (Covid-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, Hubei Province, China in late December, the cases of Covid-19 have spiralled out around the globe. Due to the clinical similarity of Covid-19 with other flulike syndromes, patients are assayed for other pathogens of influenza like illness. There have been reported cases of co-infection amongst patients with Covid-19. Bacteria for example Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia,…
There is a near consensus view that SARS-CoV-2 has a natural zoonotic origin; however, several characteristics of SARS-CoV-2 taken together are not easily explained by a natural zoonotic origin hypothesis. These include: a low rate of evolution in the early phase of transmission; the lack of evidence of recombination events; a high pre-existing binding to human ACE2; a novel furin cleavage site insert; a flat glycan binding domain of the spike protein which conflicts with host evasion survival patterns exhibited by other coronaviruses, and high human and mouse peptide mimicry. Initial assumpti…
Human genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomics-guided maps of up-stream regulatory elements, their expression and functions in human body, including pathophysiologically-relevant cell types. Genes acting as repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors (VDR; GATA5; SFTPC; HIF1a) and activators (HMGA2; INSIG1) were then employed to identify existing drugs that could b…
The emergence of new variants of SARS-CoV-2 is a major concern given their potential impact on the transmissibility and pathogenicity of the virus as well as the efficacy of therapeutic interventions. Here, we predict the mutability of all positions in SARS-CoV-2 protein domains to forecast the appearance of unseen variants. Using sequence data from other coronaviruses, pre-existing to SARS-CoV-2, we build statistical models that do not only capture amino-acid conservation but more complex patterns resulting from epistasis. We show that these models are notably superior to conservation profile…
In the present article a mathematical model is proposed to research the current coronavirus outbreak (SARS-CoV-2) in Paraguay, describing the multiple transmission paths in the infection dynamics, following the susceptible, exposed, infectious, hospitalized, with lost immunity and recovered individuals, as well as the role of the virus in the environment and deaths from COVID-19 or other reasons. In order to reflect the impact of the control measures adopted by the government and the population, the model employs variable transmission rates that change with the epidemiological status and envir…
Although lessons have been learned from previous severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) outbreaks, the rapid evolution of the viruses means that future outbreaks of a much larger scale are possible, as shown by the current coronavirus disease 2019 (COVID-19) outbreak. Therefore, it is necessary to better understand the evolution of coronaviruses as well as viruses in general. This study reports a comparative analysis of the amino acid usage within several key viral families and genera that are prone to triggering outbreaks, including coronavirus (S…
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been mutating since it was first sequenced in early January 2020. The genetic variants have developed into a few distinct clusters with different properties. Since the United States (US) has the highest number of viral infected patients globally, it is essential to understand the US SARS-CoV-2. Using genotyping, sequence-alignment, time-evolution, $k$-means clustering, protein-folding stability, algebraic topology, and network theory, we reveal that the US SARS-CoV-2 has four substrains and five top US SARS-CoV-2 mutations we…
One regards spaces of trees as stratified spaces, to study distributions of phylogenetic trees. Stratified spaces with may have cycles, however spaces of trees with a fixed number of leafs are contractible. Spaces of trees with three leafs, in particular, are spiders with three legs. One gives an elementary proof of the stickiness of intrinsic sample means on spiders. One also represents four leafs tree data in terms of an associated Petersen graph. One applies such ideas to analyze RNA sequences of SARS-CoV-2 from multiple sources, by building samples of trees and running nonparametric statis…
Coronavirus disease 2019 (COVID-19) is a continuously devastating public health and the world economy. One of the major challenges in controlling the COVID-19 outbreak is its asymptomatic infection and transmission, which are elusive and defenseless in most situations. The pathogenicity and virulence of asymptomatic COVID-19 remain mysterious. Based on the genotyping of 20656 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) genome isolates, we reveal that asymptomatic infection is linked to SARS-CoV-2 11083G>T mutation, i.e., leucine (L) to phenylalanine (F) substitution at the res…
Accurate and reliable forecasting of emerging dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants enables policymakers and vaccine makers to get prepared for future waves of infections. The last three waves of SARS-CoV-2 infections caused by dominant variants Omicron (BA.1), BA.2, and BA.4/BA.5 were accurately foretold by our artificial intelligence (AI) models built with biophysics, genotyping of viral genomes, experimental data, algebraic topology, and deep learning. Based on newly available experimental data, we analyzed the impacts of all possible viral spike (S)…
The novel coronavirus SARS-CoV-2 has rapidly emerged as a significant threat to global public health, in particular because -- as is not uncommon with novel pathogens -- there is no effective pharmaceutical treatment or prophylaxis to the viral syndrome it causes. In the absence of such specific treatment modalities, the mainstay of public health response rests on non-pharmaceutical interventions (NPIs), such as social distancing. This paper contributes to the understanding of social distancing against SARS-CoV-2 by quantitatively analysing the statistical dynamics of disease propagation as a …
Background: The analysis of the Sars-CoV-2 epidemic is of paramount importance to understand the dynamics of the coronavirus spread. This can help health and government authorities take the appropriate measures and implement suitable politics aimed at fighting and preventing it. Methods: A time-dependent dynamic SEIR model inspired in a model previously used during the MERS outbreak in South Korea was used to analyse the time trajectories of active and hospitalized cases in Portugal. Results: The time evolution of the virus spread in the country was adequately modelled. The model has changeabl…
Understanding the number of individuals who have been infected with the novel coronavirus SARS-CoV-2, and the extent to which social distancing policies have been effective at limiting its spread, are critical for effective policy going forward. Here we present estimates of the extent to which confirmed cases in the United States undercount the true number of infections, and analyze how effective social distancing measures have been at mitigating or suppressing the virus. Our analysis uses a Bayesian model of COVID-19 fatalities with a likelihood based on an underlying differential equation mo…
The devastating impact of the COVID-19 pandemic caused by SARS coronavirus 2 (SARS CoV 2) has raised important questions about viral origin, mechanisms of zoonotic transfer to humans, whether companion or commercial animals can act as reservoirs for infection, and why there are large variations in SARS-CoV-2 susceptibilities across animal species. Powerful in silico modelling methods can rapidly generate information on newly emerged pathogens to aid countermeasure development and predict future behaviours. Here we report an in silico structural homology modelling, protein-protein docking, and …
The coronavirus disease (COVID-19) pandemic has changed our lives and still poses a challenge to science. Numerous studies have contributed to a better understanding of the pandemic. In particular, inhalation of aerosolised pathogens has been identified as essential for transmission. This information is crucial to slow the spread, but the individual likelihood of becoming infected in everyday situations remains uncertain. Mathematical models help estimate such risks. In this study, we propose how to model airborne transmission of SARS-CoV-2 at a local scale. In this regard, we combine microsco…
In a previous article [1] we have described the temporal evolution of the Sars- Cov-2 in Italy in the time window February 24-April 1. As we can see in [1] a generalized logistic equation captures both the peaks of the total infected and the deaths. In this article our goal is to study the missing peak, i.e. the currently infected one (or total currently positive). After the April 7 the large increase in the number of swabs meant that the logistical behavior of the infected curve no longer worked. So we decided to generalize the model, introducing new parameters. Moreover, we adopt a similar a…
SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this, outbreak specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico…
Originating in Wuhan, the novel coronavirus, severe acute respiratory syndrome 2 (SARS-CoV-2), has astonished health-care systems across globe due to its rapid and simultaneous spread to the neighboring and distantly located countries. To gain the systems level understanding of the role of global transmission routes in the COVID-19 spread, in this study, we have developed the first, empirical, global, index-case transmission network of SARS-CoV-2 termed as C19-TraNet. We manually curated the travel history of country wise index-cases using government press releases, their official social media…
The dense social contact networks and high mobility in congested urban areas facilitate the rapid transmission of infectious diseases. Typical mechanistic epidemiological models are either based on uniform mixing with ad-hoc contact processes or need real-time or archived population mobility data to simulate the social networks. However, the rapid and global transmission of the novel coronavirus (SARS-CoV-2) has led to unprecedented lockdowns at global and regional scales, leaving the archived datasets to limited use. While it is often hypothesized that population density is a significant driv…
