In-silico study for the screening and preparation of ionic liquid-AVDs conjugate to combat COVID-19 surge.

The pandemic due to COVID-19 caused by SARS-CoV-2 has led to the recorded deaths worldwide and is still a matter of concern for scientists to find an effective counteragent. The combination therapy is always been a successful attempt in treating various threatful diseases. Recently, Ionic liquids (ILs) are known for their antiviral activity. Fascinating tunable properties of ILs make them a potential candidate for designing the therapeutic agent. The concern while using ILs in biomedical field remains is toxicity therefore, choline-based ILs were used in the study as they are considered to be greener as compared to other ILs. In the present study strategically, we performed the blind molecular docking of antiviral drug (Abacavir, Acyclovir, and Galidesivir)-choline based ILs conjugates with the target protein (Mpro protease). The molecules were screened on the basis of binding energy. The data suggested that the combination of AVDs-ILs have greater antiviral potential as compared to the drugs and ILs alone. Further, the ADME properties and toxicity analysis of the screened conjugates was done which revealed the non-toxicity of the conjugates. Additionally, the energetic profiling of the ILs drugs and their conjugates was done using DFT calculations which revealed the stability of the conjugates and have a better option to be developed as a therapeutic agent. Also, from molecular dynamic simulation was done and results showed the stability of the complex formed between target protein and the designed conjugates of AVDs and ILs.

A computational approach for the screening of potential antiviral compounds against SARS-CoV-2 protease: Ionic liquid vs herbal and natural compounds.

The current scenario across the globe shows unprecedented healthcare and an economic crisis due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recently, the World Health Organization (WHO) has declared a pandemic stage worldwide because of the high mortality and morbidity rate caused by novel infection disease. There have been several clinical trials and identification underway to find a treatment of this novel virus. For the treatment of severe infection involves the blocking of the replication of its CoV-2 protein. Hydroxychloroquine and remdesivir has been used on an emergency basis for its treatment. The uncontrolled infection and increasing death rate underline the emergence to develop the antiviral drug. In our study, the blind docking of various classes of compounds including control antiviral drugs (abacavir, acyclovir, quinoline, hydroxyquinoline), antimicrobial drugs (levofloxacin, amoxicillin, cloxacin, ofloxacin), natural compounds (lycorine, saikosaponins, myricetin, amentaflavone), herbal compounds (silymarin, palmatine, curcumin, eugenin) available in Indian Ayurveda was done. Besides, we have also performed the blind docking of various ionic liquids (ILs) such as pyrrolidinium, piperidinium, pyridinium, imidazolium based ILs against CoV-2 protease as they have recently emerged as a potential antimicrobial agent. Further, the pharmacokinetic properties and cytotoxicity of the compounds were determined computationally. The docking results showed successful binding to the active site or near a crucial site. The present computational approach was found helpful to predict the best possible inhibitor of protease and may result in an effective therapeutic agent against COVID-19.