SARS-CoV-2 is a newly emerged coronavirus that causes a respiratory disease with variable severity and fatal consequences. It was first reported in Wuhan and subsequently caused a global pandemic. The viral spike protein binds with the ACE-2 cell surface receptor for entry, while TMPRSS2 triggers its membrane fusion. In addition, RNA dependent RNA polymerase (RdRp), 3′–5′ exoribonuclease (nsp14), viral proteases, N, and M proteins are important in different stages of viral replication. Accordingly, they are attractive targets for different antiviral therapeutic agents. Although many antiviral agents have been used in different clinical trials and included in different treatment protocols, the mode of action against SARS-CoV-2 is still not fully understood. Different potential repurposed drugs, including, chloroquine, hydroxychloroquine, ivermectin, remdesivir, and favipiravir, were screened in the present study. Molecular docking of these drugs with different SARS-CoV-2 target proteins, including spike and membrane proteins, RdRp, nucleoproteins, viral proteases, and nsp14, was performed. Moreover, the binding affinities of the human ACE-2 receptor and TMPRSS2 to the different drugs were evaluated. Molecular dynamics simulation and MM-PBSA calculation were also conducted. Ivermectin and remdesivir were found to be the most promising drugs. Our results suggest that both these drugs utilize different mechanisms at the entry and post-entry stages and could be considered potential inhibitors of SARS-CoV-2 replication.

The phytochemical analysis of the ethyl acetate fraction of Arum palaestinum Boiss. (Araceae) led to the isolation and identification of a new polyhydroxy alkaloid compound; (S)-3,4,5-trihydroxy-1 H-pyrrol-2(5H)-one (1), and other five known compounds; caffeic acid (2), isoorientin (3), luteolin (4) and vicenin 11 (5), as well as the rare compound 3,6,8-trimethoxy, 5,7,3',4'-tetrahydroxy flavone (6). The structural elucidations of all the compounds were based on spectroscopic data (1H- and 13C-NMR, DEPT, HSQC, HMBC and NOE difference techniques) and comparison with literature data. Investigation of the antioxidant activity of the ethyl acetate fraction indicated its strong scavenging capacity for 1,1 -diphenyl-2-picrylhydrazyl (DPPH) radicals (SC50 3.1+/-0.82 microg/mL). Moreover, the treatment of different human cancer cell lines with the ethyl acetate fraction led to dose-dependant suppression in the proliferation of both breast carcinoma cells (MCF-7; IC50 59.09+/-4.1 microg/mL) and lymphoblastic leukemia cells (1301; IC50 53.1+/-2.9 microg/mL); however, it was found to have no effect on the growth of hepatocellular carcinoma cells (Hep G2).

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Schistosomiasis control is widely dependent on a single drug, praziquantel (PZQ). The potential for development of resistance to PZQ has justified the search for new alternative chemotherapies. In a previous study, we have been reported that three of 8-hydroxyquinoline derivatives namely: 3-((8-hydroxyquinolin-5-yl) sulfonyl) pentane-2,4-dione (HQSP), 5-((2,4-diphenyl-3H-benzo[b][1,4]diazepin-3-yl) sulfonyl) quinolin-8-ol (HQBD), and 5-((2,4-diphenyl-3H-pyrido[3,4-b][1,4] diazepin-3-yl) sulfonyl) quinolin-8-ol (HQPD) possess a potent anti-schistosomal activity in vitro. The aim of the present study was to evaluate the in vivo schistosomicidal effect of these three compounds on adult and immature worms of Schistosoma mansoni and their induced pathology. Treatment of S. mansoni-infected mice with 1000, 250, 150, and 200 mg/kg body weight of PZQ, HQSP, HQBD, and HQPD, respectively, reduced adult and immature worm burden by 94.63 and 31.32%, 73.63 and 5.45%, 76.5 and 28.11%, and 81.25 and 56.84%, respectively, compared to infected untreated mice. Moreover, numbers of egg per gram liver and intestine were decreased by 84 and 95.51%, 47.84 and 46.28 %, 53.18 and 59.37 %, and 54.22 and 67.26 as a result of PZQ, HQSP, HQBD, and HQPD treatment, respectively. Hepatic granuloma volume was also reduced by 40.10, 42.96, 35.72, and 72.09% due to PZQ, HQSP, HQBD, and HQPD treatment, respectively. In addition, hepatic histopathological alterations and collagen fiber deposition that accompanied with S. mansoni infection were largely retrieved with different treatments, especially HQPD treatment. Furthermore, humoral immune response, especially IgG response against S. mansoni antigens, was augmented with different treatments. This study concluded that among the three tested 8-hydroxyquinoline derivatives, HQPD is the most effective compound against adult and pre-mature worms of S. mansoni and can be used for the development of a new schistosomicidal drug.