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The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised global health concerns. RNA-dependent RNA polymerase (RdRp) is the prime component of viral replication/proliferation machinery and is considered to be a potential drug target against SARS-CoV-2. The present study investigated the anti-RdRp activity of phytochemicals against SARS-CoV-2 infection. Virtual ligand screening was carried out to determine the potent compounds against RdRp. Molecular docking and an MD Simulation study were employed to evaluate the spatial affinity of selected phytochemicals for the active sites of RdRp. Structural stability of target compounds was determined using root mean square deviation computational analysis and drug-like abilities were investigated using ADMET. Bond distances between ligand and receptor were marked to predict the strength of interaction. Aloe, azadirachtin, columbin, cirsilineol, nimbiol, nimbocinol and sage exhibited the highest binding affinities and interacted with active sites of RdRp, surpassing the ability of chloroquine, lamivudine, favipiravir and remdesivir to target the same. All the natural metabolites exhibited stable conformation during MD Simulation of 101 ns at 310 K. Kinetic, potential and electrostatic energy were observed to be least in the case of natural metabolites in comparison with synthetic analogues. Deviations and fluctuations were observed to be structurally least in target phytochemicals. Physiochemical and biological properties of these compounds further validated their drug-like properties. Non-bonded distance was found to be short enough to form hydrogen bonding or hydrophobic interactions, which revealed that these target compounds can strongly bind with RdRp. The study found potential phytochemicals to disrupt the replication domain of SARS-CoV-2 by hindering RdRp. We therefore anticipate that the current findings could be considered as valuable for the development of an efficient preventive/therapeutic expedient against COVID-19.

A 72-year-old female and a 57-year-old male with chronic hepatitis C were treated with a combination therapy of pegylated interferon (PEG-IFN)-α 2a (180 µg s.c. once a week) and ribavirin (1,000 mg orally daily). This resulted in the destruction of melanocytes at the injection site in both patients. In the male patient, the depigmentation progressed to the surrounding skin area. The dermatologist concurred with vitiligo as the diagnosis in both patients. Injection and surrounding site vitiligo associated with PEG-IFN-α 2b treatment for hepatitis C was noticed in previous case studies. For the first time, the case reports below highlight the same immunological adverse event secondary to PEG IFN-α 2a/ribavirin combination therapy and explain, in part, the complex interaction between host immune response and viral genotype. In addition, we systematically review drug-induced vitiligo and autoimmune diseases associated with the depigmentation disorder.

The pharmacokinetics of scorpion venom and its toxins has been investigated in experimental models using adult animals, although, severe scorpion accidents are associated more frequently with children. We compared the effect of age on the pharmacokinetics of tityustoxin, one of the most active principles of Tityus serrulatus venom, in young male/female rats (21-22 days old, N = 5-8) and in adult male rats (150-160 days old, N = 5-8). Tityustoxin (6 µg) labeled with 99mTechnetium was administered subcutaneously to young and adult rats. The plasma concentration vs time data were subjected to non-compartmental pharmacokinetic analysis to obtain estimates of various pharmacokinetic parameters such as total body clearance (CL/F), distribution volume (Vd/F), area under the curve (AUC), and mean residence time. The data were analyzed with and without considering body weight. The data without correction for body weight showed a higher Cmax (62.30 ± 7.07 vs 12.71 ± 2.11 ng/ml, P < 0.05) and AUC (296.49 ± 21.09 vs 55.96 ± 5.41 ng h-1 ml-1, P < 0.05) and lower Tmax (0.64 ± 0.19 vs 2.44 ± 0.49 h, P < 0.05) in young rats. Furthermore, Vd/F (0.15 vs 0.42 l/kg) and CL/F (0.02 ± 0.001 vs 0.11 ± 0.01 l h-1 kg-1, P < 0.05) were lower in young rats. However, when the data were reanalyzed taking body weight into consideration, the Cmax (40.43 ± 3.25 vs 78.21 ± 11.23 ng kg-1 ml-1, P < 0.05) and AUC (182.27 ± 11.74 vs 344.62 ± 32.11 ng h-1 ml-1, P < 0.05) were lower in young rats. The clearance (0.03 ± 0.002 vs 0.02 ± 0.002 l h-1 kg-1, P < 0.05) and Vd/F (0.210 vs 0.067 l/kg) were higher in young rats. The raw data (not adjusted for body weight) strongly suggest that age plays a pivotal role in the disposition of tityustoxin. Furthermore, our results also indicate that the differences in the severity of symptoms observed in children and adults after scorpion envenomation can be explained in part by differences in the pharmacokinetics of the toxin.