COVID-19 Research: Interesting COVID-19 Pre-Print Non-Peer Reviewed Research Studies Worth Exploring (Vol 3)
: This is Thailand Medical News third installment of a new weekly series of articles on various pre-print research studies that have been published on numerous servers but have yet to have been peer-reviewed. Most will warrant further research but these are some of the selected studies that we feel need to be explored in detail further.
1. Emerging viral mutants in Australia suggest RNA recombination event in the SARS-CoV-2 (COVID-19) genome
This Australian study warns that the RNA strand in the SARS-CoV-2 coronavirus has a high affinity for recombining with pieces of other RNA strands from the host or even other viruses. Because a high frequency of recombination events in coronaviruses occur, RNA recombination could lead to either enhance the adaptation process to its new host like human or cause unpredictable changes in virulence during infection.
2. Potential Phytochemical Inhibitors of the Coronavirus RNA Dependent RNA Polymerase: A Molecular Docking Study
Indian researchers using molecular docking study platforms identify three phytochemicals that have a very high binding affinity to the SARS-CoV-2 coronavirus. Their results show that various phytochemical constituents from Withania somnifera
root extract, Hyssopus officinalis
and Camellia sinensis
leaf extract have high binding affinity towards spike proteins RdRps and are comparable to the small molecule drug remdesivir. Their binding interactions reveal that they bind to the amino acid residues involved in nucleoside triphosphate (NTP) entry and recognition site and metal ion cofactor chelating site of both SARS-CoV-2 and SARS-CoV. Hence they are different from the classical nucleotide analog inhibitors of RdRp. This study paves a quick platform for development of targeted therapy using phytochemicals for COVID-19 and other potential SARS coronavirus related outbreaks in future.
3. Not even the air of empty spaces is coronavirus free (Two meters is not a safe distance)
This Brazilian study warns that the contagion in present in the air several hours even after an infected individual has been in a room and it also warns about the effects of air-conditioners in helping to spread the coronavirus.
4. Luteolin: A Dietary Molecule as Potential Anti-COVID-19 Agent
Another study involving molecular docking platform studies but this identifies a flavonoid called Luteolin. Luteolin (Lut) is
an important plant-derived flavonoid that is widely distributed in edible herbs and vegetables. Studies on animal and human models have shown that Lut exhibits various pharmacological properties, viz. anti-inflammatory, anti-cancer, anti-oxidant, anti-apoptotic, and neurotrophic actions. Several studies have explained the protective nature of Lut by inhibiting virus entry and fusion with human receptors in old SARS-CoV that had emerged in 2003. Thus, regular consumption of foods having adequate amount of Lut in our diet may be helpful in inhibiting the SARS-CoV-2 infection as well and may prevent the consequent symptoms in COVID-19 patients. In present work, we have carried out the molecular docking studies of Lut with six different SARS-CoV-2 encoded key proteins. The FDA-approved drug remdesivir was also evaluated as control to compare the results. Lut showed excellent inhibitory action against papain-like proteinase, a main protease of SARS-CoV-2. Lut was also many times more active than remdesivir. Therefore, the foods which have Lut in adequate amount might be explored further for potential use against COVID-19 https://www.researchsquare.com/article/rs-35368/v1
5. Crystal structure of SARS-CoV-2 main protease in complex with a Chinese herb inhibitor Shikonin
This Chinese study explores using a traditional Chinese medicine herb called Shikonin. The main protease (Mpro, also known as 3CLpro) has a major role in the replication of coronavirus life cycle and is one of the most important drug targets for anticoronavirus agents. In this study, the researchers report the crystal structure of main protease of SARS-CoV-2 bound to the identified Chinese herb inhibitor shikonin at 2.45 angstrom resolution. Although the structure revealed here shares similar overall structure with other published structures, there are several key differences which highlight potential features that could be exploited. The catalytic dyad His41-Cys145 undergoes dramatic conformational changes, and the structure reveals an unusual arrangement of oxyanion loop stabilized by the substrate. Binding to shikonin and binding of covalent inhibitors show different binding modes, suggesting diversity in inhibitor binding. This could the pave for more research as to how to harness the antiviral properties of the herb to treat COVID-19. https://www.biorxiv.org/content/10.1101/2020.06.16.155812v1
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