A complete overview on the COVID-19 pandemic five months after the initial outbreak in Wuhan, China, started December 2019. Information on epidemiology, pathogenesis, pathology, clinical features, detection methods and treatment.
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The aminoquinolines chloroquine and hydroxychloroquine are used for treatment of malaria and rheumatic diseases and were recently suggested as effective therapy against coronavirus disease 2019 (COVID 19) due to their anti-inflammatory and antiviral effects. In the United States, the Food and Drug Administration issued an Emergency Use Authorization on March 30, 2020 allowing the use of these drugs in patients with COVID-19 who were not enrolled in clinical trials. However, to date, there have been no robust clinical trials proving efficacy of these agents in such a disease. Not only the available data comes from small studies which lack proper control but also are underpowered to detect meaningful clinical effects.
PAC-MAN (prophylactic antiviral CRISPR in human cells), a Cas13-based strategy, can effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus in human lung epithelial cells. The authors designed and screened CRISPR RNAs covering conserved viral regions and identified 6 crRNAs capable of targeting more than 90% of all coronaviruses. Therefore, PAC-MAN can be a potential pan-coronavirus inhibition strategy.
Resolving SARS-CoV-2 protein structures is essential to develop appropriate and specific pharmacological intervention to fight the current CoViD-19 pandemic. The RNA-dependent RNA polymerase (RdRp, also called Nsp12) is the central component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug Remdesivir. Notably, the resolved structure of RdRp can also serve as a model to design new active compounds targeting Nsp12.
Mpro is a key SARS-CoV-2 enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target. Currently, there are no targeted therapeutics against SARS-CoV-2 and effective treatment options remain very limited. In order to rapidly discover lead compounds for clinical use, the authors of this mini-review performed a different set of virtual screening, such as combined structure-assisted drug design, virtual drug screening and high-throughput screening, to identify new or existing drugs targeting the CoViD-19 virus main protease.
Analysis of the SARS-CoV-2 Spike protein (S) and mapping of the unique glycan-processing sites across the trimeric viral spike. These insights will be useful in clinical evaluation and control of candidate vaccines.
Independent studies suggest that the virus responsible of the current CoViD-19 pandemic originated from a genetic reshuffling of pangolin and bat CoV-like viruses. While bats may be the reservoir host for various Coronaviruses, this study further indicates that pangolins are likely to have acted as an intermediate host of SARS-CoV-2. These animals, illegally smuggled from and to various Countries, could represent a potential future threat to public health if the wildlife trade is not efficiently controlled.