Background: The natural products have played a major role in combating diseases including the viral diseases. Rhazya stricta Decne belongs to the family Apocynaceae and found abundantly in various parts of Pakistan. The plant is known for its use in the folk medicine system for the treatment of various diseases. The wide spectrum of the biological properties of the plant include antiviral, antidiabetic, antifungal, antibacterial and anticancer. Over 250 chemical constituents have been reported from the plant including over 100 alkaloids from different parts of the plant. Several alkaloids and non-alkaloid have also shown a variety of biological activities including the antiviral activities. Several active chemical constituents have been reported from different part of the plant. The extracts of the plant have also shown activities against influenza virus. As influenza viruses have developed resistance to available therapies to cope with the virus, it may become another threat like the coronavirus pandemic. Under the circumstances, new therapies are badly needed to meet the growing challenge of the viruses.
Material and Method: The extracts of different parts of the plant were subjected to various bioassays to determine their biological activities. The computer-simulated experiments are becoming one of the effective methods used in drug discovery; enabling the simulation of drug-biological target dynamics, prediction of drug efficacy and design of novel drug molecules within a virtual environment. The extracts of the leaves of the plant were investigated for their antiviral activities in vitro to find out their effectiveness against the viral diseases including the influenza viruses and also to identify promising chemical constituents ‘In silico’. The extracts were subjected to in vitro experiments by using Madin-Darby Canine Kidney cell line (MDCK) as a substrate for the influenza virus and estimating the inhibition performance of the extracts of the leaves of the plant. The ‘In silico’ screening was also carried out to determine the antiviral activities of the plant. The extract of the leaves of the plant was subjected to the MTT say to determine its cytotoxicity as well as antiviral activity against influenza virus. The extract of the leaves of the plant was also subjected to time-of-addition assay to determine mechanism of action of the extract during the life cycle of the virus. The ‘In silico’ studies analyses were performed, including the molecular docking, drug-likeness analysis, and toxicity risk assessment were conducted to find out state the lead compounds to be developed into an antiinfluenza virus drug. The extract of the plant may prove effective remedy against the influenza virus and may be used to develop drug to deal with the influenza viruses.
Results: The extracts of various parts of Rhazya stricta have shown antiviral properties in in vitro and in vivo experiments. The extracts of the plant have shown potent activity against influenza virus. Keeping in view the potential of the plant against influenza virus, it may be further investigated for its use in treating the viral diseases including the influenza virus and also to develop an effective drug to control the viral diseases including the influenza virus. The ‘In silico’ experiments were performed to find out toxicity and antiviral and anti-influenza therapy of the extracts of the leaves of the plant. The doses of the extract of the leaves of the plant at 184.6 µg/ml and 19.71 µg/ml proved to be 50% cytotoxicity concentration and 50% inhibition concentration, respectively. The time of addition assay showed that the extract of the leaves of the plant exerted its activity in the late step of the influenza virus replication cycle. In comparison to Oseltamivir, the lead compounds showed better binding affinity and may be developed into oral drugs with low toxicity risk. Isolation and purification of the lead compounds and testing their antiviral activity in vitro and in vivo are required.
Conclusion: The extracts of Rhazya stricta have shown strong antiviral activities and can effectively treat the coronavirus and influenza viruses. The researches lead to the conclusion that the extracts of the plant could be used as a source for modern and effective antiviral agents and help threatened mankind in the viral resistance battle. The in vitro study followed by computational investigations revealed that the extract of the leaves of the plant possess the antiviral potential. The extracts of the leaves of the plant also showed their effectiveness in treating the influenza virus. Further researches, including the in vitro and in vivo studies are required to analyze the extracts of the plant and its constituents for their antiviral activities.