arXiv subjects

Mohammad Reza Dayer

Publications and source records attributed to Mohammad Reza Dayer.

3 recordsLinked to original sources

arXiv2021

New Candidates for Furin Inhibition as Probable Treat for COVID-19: Docking Output

Furin is a serine protease that takes part in the processing and activation of the host cell pre-proteins. The enzyme also plays an important role in the activation of several viruses like the newly emerging SARS-CoV-2 virus that causes COVID-19 disease with a high rate of virulence and mortality. Unlike viral enzymes, furin owns a constant sequence and active site characteristics and seems to be a better target for drug design for COVID-19 treatment. Considering furin active site as receptor and some approved drugs from different classes including antiviral, antibiotics, and anti protozoa/anti parasites with suspected beneficial effects on COVID-19, as ligands we have carried out docking experiments in HEX software to pickup those capable to bind furin active site with high affinity and suggest them as probable candidates for clinical trials assessments. Our docking experiments show that saquinavir, nelfinavir, and atazanavir with cumulative inhibitory effects of 2.52, 2.16, and 2.13 respectively seem to be the best candidates for furin inhibition even in severe cases of COVID-19 as adjuvant therapy, while clarithromycin, niclosamide, and erythromycin with cumulative inhibitory indices of 1.97, 1.90, and 1.84 respectively with lower side effects than antiviral drugs could be suggested as prophylaxes for the first stage of COVID-19 as a promising treat.

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arXiv2020

Old Drugs for JAK-STAT Pathway Inhibition in COVID-19

The pandemic threat of COVID-19 with more than 37 million cases in which about 5 percent entering critical stage characterized by cytokine storm and hyperinflammatory condition, the state more often leads to admission to intensive care unit with rapid mortality. Janus kinase enzymes of Jak-1, Jak-2, Jak-3, and Tyk2 seem to be good targets for inhibition by medications to control cytokine storm in this context. In the present work, the inhibitory properties of different analgesic drugs on these targets are studied to assess their ability for clinical application from different points of view. Our docking results indicated that naproxen, methadone, and amitriptyline considering their higher binding energy, lower energy variance, and higher hydrophobicity, seem to express more inhibitory effects on Janus kinase enzymes than thats for approved inhibitors i.e. baricitinib and ruxolitinib. Accordingly, we suggest our wide list of candidate drugs including indomethacin, etodolac, buprenorphine, rofecoxib, duloxetine, valdecoxib, naproxen, methadone, and amitriptilin for clinical assessments for their usefulness in COVID-19 treatment, especially taking into account that up to now, there is no approved cure for this disease.

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arXiv2020

Old Drugs for Newly Emerging Viral Disease, COVID-19: Bioinformatic Prospective

Coronavirus (COVID-19) outbreak in late 2019 and 2020 comprises a serious and more likely a pandemic threat worldwide. Given that the disease has not approved vaccines or drugs up to now, any efforts for drug design and or clinical trails of old drugs based on their mechanism of action are worthy and creditable in such circumstances. Experienced docking experiments using the newly released coordinate structure for COVID-19 protease as a receptor and thoughtfully selected chemicals among antiviral and antibiotics drugs as ligands may be leading in this context. We selected nine drugs from HIV-1 protease inhibitors and twenty-one candidates from anti bronchitis drugs based on their chemical structures and enrolled them in blind and active site-directed dockings in different modes and in native-like conditions of interactions. Our findings suggest the binding capacity and the inhibitory potency of candidates are as follows Tipranavir>Indinavir>Atazanavir>Darunavir>Ritonavir>Amprenavir for HIV-1 protease inhibitors and Cefditoren>Cefixime>Erythromycin>Clarithromycin for anti bronchitis medicines. The drugs bioavailability, their hydrophobicity and the hydrophobic properties of their binding sites and also the rates of their metabolisms and deactivations in the human body are the next determinants for their overall effects on viral infections, the net results that should survey by clinical trials to assess their therapeutic usefulness for coronavirus infections.

q-bio.BM↗