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AbstractInfluenza virus is the cause of the death of millions of people with about 3–4 pandemics every hundred years in history. It also turns into a seasonal disease, bringing about approximately 5–15% of the population to be infected and 290,000–650,000 people to die every year. These numbers reveal that it is necessary to be on the alert to work towards influenza in order to protect public health. There are FDA-approved antiviral drugs such as oseltamivir and zanamivir recommended by the World Center for Disease Prevention. However, after the recent outbreaks such as bird flu and swine flu, increasing studies have shown that the flu virus has gained resistance to these drugs. So, there is an urgent need to find new drugs effective against this virus. This study aims to investigate new drug candidates targeting neuraminidase (NA) for the treatment of influenza by using computer aided drug design approaches. They involve virtual scanning, de novo design, rational design, docking, MD, MMGB/PBSA. The investigation includes H1N1, H5N1, H2N2 and H3N2 neuraminidase proteins and their mutant variants possessing resistance to FDA-approved drugs. Virtual screening consists of approximately 30 thousand molecules while de novo and rational designs produced over a hundred molecules. These approaches produced three lead molecules with binding energies for both non-mutant (-34.84, −59.99 and −60.66 kcal/mol) and mutant (-40.40, −58.93, −76.19 kcal/mol) H2N2 NA calculated by MM-PBSA compared with those of oseltamivir −25.64 and −18.40 respectively. The results offer new drug candidates against influenza infection.Communicated by Ramaswamy H. Sarma

In the present article we consider infinite locally finite perfect groups that are product of proper normal soluble subgroups of derived length at most n(ΠSn-groups for short) for some fixed positive integer nand give structural results for these groups. Also we provide some consequences for certain locally finite minimal non-X-groups for some classes Xand barely transitive groups in the context mentioned above. Furthermore, we define certain collections of groups and consider their intersection with ΠSn. Finally, we investigate some groups which have non-trivial minimal non-FCepimorphic images.

AbstractHIV-1, a member of Retroviruses’ Lentivirus family, is the causative agent of AIDS. The virus is common throughout the world and leaves the body vulnerable to infections by suppressing the human immune system. Reverse transcriptase and integrase are two of three HIV-1 essential enzymes which perform important virus life cycle functions. In recent years, researchers started to design new inhibitors which could inhibit multiple targets for treatment of AIDS. In respect to this, RT and IN are two enzymes suitable for the development of dual inhibitors. To realize this aim, here we have designed new inhibitors by using approved reverse transcriptase and integrase inhibitors as drug design templates. Totally 426 ligands, which are filtered from 858 ligands by druggability properties were docked to crystal structure of reverse transcriptase and since there was no full-length structure of HIV-1 IN, same ligands were docked to Prototype Foamy Virus integrase structure. From the docking results, B099 was determined to be the best binding ligand to RT enzyme with a binding free energy of −12.63 kcal/mole and B249 was the best ligand for IN enzyme with a score of −19.83 kcal/mole. These binding scores demonstrate that these ligands are more active than Raltegravir for integrase and Rilpivirine for reverse transcriptase which are also used for docking method validation. B205, B214, B233, B242, B246, B249, B253 and B254 are the some of ligands found to have good binding scores for both enzymes and could be considered as new inhibitor candidates as dual inhibitors.Communicated by Ramaswamy H. Sarma

COVID-19 has affected millions of people. Although many drugs are in use to combat disease, there is not any sufficient treatment yet. Having critical role in propagation of the novel coronavirus (SARS-CoV-2) works Main Protease up into a significant drug target. We have performed a molecular docking study to define possible inhibitor candidates against SARS-CoV-2 Main Protease enzyme.Besides docking Remdesivir, Ribavirin, Chloroquine and 28 other antiviral inhibitors (totally 31 inhibitors) to Main Protease enzyme, we have also performed a molecular docking study of 2177 ligands, which are used against Main Protease for the first time by using molecular docking program Autodock4. All ligands were successfully docked into Main Protease enzyme binding site. Among all ligands, EY16 coded ligand which previously used as EBNA1-DNA binding blocker candidate showed the best score for Main Protease with a binding free energy of -10.83 kcal/mol which was also lower than re-docking score of N3 ligand (-10.72 kcal/mol) contained in crystal structure of Main Protease. After analyzing the docking modes and docking scores we have found that our ligands have better binding free energy values than the inhibitors in use of treatment. We believe that further studies such as molecular dynamics or Molecular Mechanic Poisson Boltzmann Surface Area studies can make contribution that is more exhaustive to the docking results.