Based on our estimates of Rt, assuming SARS-like variation, we calculated that in locations with similar transmission potential to Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population. We estimated that the median daily reproduction number (Rt) in Wuhan declined from 2♳5 (95% CI 1♱5–4♷7) 1 week before travel restrictions were introduced on Jan 23, 2020, to 1♰5 (0♴1–2♳9) 1 week after. We used an additional two datasets for comparison with model outputs: daily number of new exported cases from Wuhan (or lack thereof) in countries with high connectivity to Wuhan (ie, top 20 most at-risk countries), by date of confirmation, as of and data on new confirmed cases reported in Wuhan between Jan 16, 2020, and Feb 11, 2020. The four datasets we fitted to were: daily number of new internationally exported cases (or lack thereof), by date of onset, as of daily number of new cases in Wuhan with no market exposure, by date of onset, between Dec 1, 2019, and daily number of new cases in China, by date of onset, between Dec 29, 2019, and and proportion of infected passengers on evacuation flights between Jan 29, 2020, and Feb 4, 2020. To estimate the early dynamics of transmission in Wuhan, we fitted a stochastic transmission dynamic model to multiple publicly available datasets on cases in Wuhan and internationally exported cases from Wuhan. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas. We combined a stochastic transmission model with data on cases of coronavirus disease 2019 (COVID-19) in Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January, 2020, and February, 2020.
We used these estimates to assess the potential for sustained human-to-human transmission to occur in locations outside Wuhan if cases were introduced. Combining a mathematical model of severe SARS-CoV-2 transmission with four datasets from within and outside Wuhan, we estimated how transmission in Wuhan varied between December, 2019, and February, 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas. We hypothesize that the ORF8 protein may be a non-canonical RdRp in SARS-CoV-2 with ability to bind to canonical nsp12 complex.Īn outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to 95 333 confirmed cases as of March 5, 2020. The high affinity of the adenosine analogue yields critical information about the non-canonical RNA dependent RNA polymerase (RdRp) function of ORF8 protein. Remdesivir had the highest binding affinity to ORF8 protein of SARS-CoV-2. Further, we studied the binding efficacy of various antiviral drugs against the modelled ORF8 of SARS-CoV-2 (mORF8) to repurpose the drug and to use them as a probe to study its function by studying the binding/active sites interaction. The modelled SARS-CoV-2 (mORF8 7A) protein shows IgG characteristic folds and thus may belong to IgG superfamily. Herein, we had modelled the ORF8 protein and studied its putative function using various substrates as a probe to determine its biological significance. The function of ORF8 protein in SARS-CoV-2 is uncertain.
From the genome sequence, most SARS-CoV-2 annotated ORF has a conserved sequence similar to SARS-CoV-1, except for ORF8 and ORF10. In silico studies support structural biologist with preliminary information to efficiently drive further studies and characterization. Global researchers have undertaken accelerated structural studies of key proteins involved in host-virus interaction, replication, and transcription. It is essential to understand the molecular players of SARS-CoV-2 to find a suitable treatment method and to develop an effective antiviral drug as early as possible. No current treatment options were successful in containing the ongoing pandemic COVID-19 caused by SARS-CoV-2.
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