IntroductionCOVID-19 (novel COronaVIrus Disease 2019) is caused by a novel pathogen that is pursued closely by all over the world after the worldwide pandemic was declared by WHO on March 11th. It has become one of the most important health problems by causing nearly 5M confirmed cases and over 300K deaths from 213 countries/regions in a couple of months (WHO, 2020a) 1 . More than 17,000 papers by the query "COVID-19" indexed in PubMed/NCBI and nearly 200 of them, as of 29th May 2020, about genome of severe acute respiratory syndrome-COronaVirus-2 (SARS-CoV-2) which is the agent responsible for the disease. Taxonomy of SARS-is an enveloped, +ssRNA virus belonging to the Coronaviridae family that are classified into 4 major genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus by phylogenetic studies and classified in the Betacoronavirus genus, Sarbecovirus and grouped as SARS-Like CoVs (Gorblenya et al., 2020). CoVs can infect many of animal 1 WHO (2020a). Coronavirus disease (COVID-2019) situation reports. [online]. Website: https://www.who.int/emergencies/diseases/ novel-coronavirus-2019/situation-reports accessed 17 May 2020].species from different genus including mammals, avians and reptiles (Gorblenya et al., 2006; Gorblenya et al., 2020). Until December 2019, there were 6 coronavirus species known as human pathogen. Four of them (229E, OC43, NL63, and HKU1) have caused common cold and others 2 worldwide outbreaks (SARS 2003; MERS 2012) over the last 20 years (Su et al., 2016; Zhu et al., 2020). Recently, a 7th coronavirus species has been discovered in December 2019 and first named as 2019 novel Coronavirus (2019 nCoV) and then as SARS-CoV-2 (Gorblenya et al., 2020). The outbreaks of CoVsAn outbreak of severe acute respiratory syndrome (SARS) was reported in November 2002. Despite patients carried symptoms of a viral infection, no pathogen causing pneumonia was identified, and in a few months, it was revealed that a novel CoV had caused this syndrome (Peiris et al., 2003). The filiation studies about SARS showed that the early cases were mostly seen among restaurant workers in Guandong Province, China and this information led researchers to suspect that transmission source of the virus might be an animal like bat or civet, that frequently consumed in that province (Zhong et al., 2003;
Malaria caused by Plasmodium vivax is a major cause of global morbidity and, in rare cases, mortality. Lactate dehydrogenase is an essential Plasmodium protein and, therefore, a potential antimalarial drug target. Ideally, drugs directed against this target would be effective against both major species of Plasmodium, P. falciparum and P. vivax. In this study, the crystal structure of the lactate dehydrogenase protein from P. vivax has been solved and is compared to the equivalent structure from the P. falciparum enzyme. The active sites and cofactor binding pockets of both enzymes are found to be highly similar and differentiate these enzymes from their human counterparts. These structures suggest effective inhibition of both enzymes should be readily achievable with a common inhibitor. The crystal structures of both enzymes have also been solved in complex with the synthetic cofactor APADH. The unusual cofactor binding site in these Plasmodium enzymes is found to readily accommodate both NADH and APADH, explaining why the Plasmodium enzymes retain enzymatic activity in the presence of this synthetic cofactor.
SARS-CoV-2 has caused COVID-19 outbreak with nearly 2 M infected people and over 100K death worldwide, until middle of April 2020. There is no confirmed drug for the treatment of COVID-19 yet. As the disease spread fast and threaten human life, repositioning of FDA approved drugs may provide fast options for treatment. In this aspect, structure-based drug design could be applied as a powerful approach in distinguishing the viral drug target regions from the host. Evaluation of variations in SARS-CoV-2 genome may ease finding specific drug targets in the viral genome. In this study, 3458 SARS-CoV-2 genome sequences isolated from all around the world were analyzed. Incidence of C17747T and A17858G mutations were observed to be much higher than others and they were on Nsp13, a vital enzyme of SARS-CoV-2. Effect of these mutations was evaluated on protein-drug interactions using in silico methods. The most potent drugs were found to interact with the key and neighbor residues of the active site responsible from ATP hydrolysis. As result, cangrelor, fludarabine, folic acid and polydatin were determined to be the most potent drugs which have potency to inhibit both the wild type and mutant SARS-CoV-2 helicase. Clinical data supporting these findings would be important towards overcoming COVID-19.
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