key: cord-0926505-sz3bji8c authors: Gandhi, Abhay Jayprakash; Rupareliya, Jalpa Deepak; Shukla, V.J.; Donga, Shilpa B.; Acharya, Rabinarayan title: An Ayurvedic Perspective along with in Silico Study of the Drugs for the Management of Sars-Cov-2 date: 2020-07-21 journal: J Ayurveda Integr Med DOI: 10.1016/j.jaim.2020.07.002 sha: 2099d2564aa0bd9e1fd72fe2e8618bc47ee952f3 doc_id: 926505 cord_uid: sz3bji8c BACKGROUND: Covid-19 is the disease caused by SARS-CoV2, it was identified in Wuhan, China, in 2019. It then extended across the globe and was termed as a pandemic in 2020. Though research work on its vaccine and drugs are carried out across the globe, it is even necessary to look over it through alternative sciences. OBJECTIVE: The objective of this study is to look over the disease through Ayurvedic perspective, analyse possible pathologies, select appropriate drugs and to study in-silico screening on these selected drugs. Materials & Methods: Available symptoms of Covid 19 were thoroughly studied and reviewed through Ayurveda classics, internet, preprints, etc. to understand the nature of the disease with the Ayurvedic perspective.The molecular Docking and Grid were generated through Pyrx Software with Autodock. The Lipinski Rule of Five data generated from Swiss ADME software and Target prediction of selected phytoconstituents were done by Swiss target prediction. RESULTS: and Discussion: In Ayurveda, Covid19 can be considered as Janapadaudhwans, Vaat-Kaphaj Sannipatik Jwara, Aupsargika Vyadhi, and Dhatupaka Awastha. In the molecular docking study, the binding energy and inhibition of 6 Gingesulphonic acid from Zingiber Officinalis (Sunthi) is greater than hydroxychloroquine and quinine. Most of the selected phytoconstituents follow the Lipinski rule of five. Target prediction of selected phytoconstituents was done on target of SARS-COV-2, humoral immunity, and antiviral activity. Every selected phytoconstituents works on minimum one of the targets. CONCLUSION: Thus, from the above results obtained from reviewing Ayurveda classics and after the virtual screening of selected drugs we can conclude that Nagaraadi Kashaya(Sunthi, Puskarmoola, Kantakari, Guduchi) may have appreciable results in combating SARS-COV-2. Thus, Nagaraadi Kashayam, a classical formulation can be a trial candidate for conducting further clinical trial. The outbreak of COVID-19, caused by the Noval Corona Virus (nCoV) that is now officially designated as Severe Acute Respiratory Syndrome-Related Coronavirus SARS-CoV-2, represents a pandemic threat to global public health. Although the epicentre of the Covid -19 outbreak in December of 2019 was located in Wuhan China, this disease has spread to more than 200 countries with over 3000 000 confirmed cases and still continuing. Ayurveda is a life science having a holistic approach in dealing with different types of diseases. It has a completely different way of looking at any new diseases. Understanding of any disease in Ayurveda is done by five elements, i.e. Hetu, Purvarupa, Rupa, Upashaya-Anupashaya, Samprapti. [1] By these elements we get to know about the nature of the diseases (Vikara Prakruti), site of the diseases (Adhisthanam), the course of the disease (Samprapti) and about the aggravating factors of the disease. By understanding these factors in detail, we can design the preventive measures and treatment protocol for the disease. Though Ayurveda focuses on the concept of individualism and accepts that each individual is unique but in this situation of the pandemic when many people are affected by the same set of symptoms, we can briefly design a treatment policy by considering the available information about the disease. Thus, it is the need of an hour to think out of the box so here is an initiation to think about the disease through Ayurveda perspective. The main objective of this study is to look over the disease through Ayurvedic perspective, analyse possible pathologies, select appropriate drugs and to study in-silico screening on these selected drugs. Though, there are many protease of the disease present but this study is limited to virtual screening against main protease (Mpro) of the virus. The present piece of work studies the virtual screening of the phytoconstituents which can help for a further invitro, invivo research for Covid 19. According to WHO, People who have co-morbidities and those over 60 years of age have a higher risk of developing severe symptoms of Covid 19. [2] Common symptoms of Covid 19 include fever (Jwar),tiredness (Shrama, Klama) and dry cough(Shushka Kasa). Other symptoms include shortness of breath (Shwasa), aches and pains (Anga Mardam), sore throat (Kantha Shoola), very few people will report diarrhoea (Drava Mala), nausea (Hrullas) or a runny nose (Peenasa). With the help of the available data regarding Covid19 and after going through the Ayurveda classics thoroughly, the following possible pathological models can be drawn. [3] Covid-19 has evolved itself into a pandemic, affecting a large population irrespective of their physical features, dietary patterns, psychological attributes, etc., Ayurveda considers it as a Janapada-Udhwamsa Vikara. [4] By looking at its symptomatology, it resembles with the classical features of Vaata Kafaja Jwaram mentioned in the classics. [6] -Covid 19 is transmitting from one human to others by direct contact (Gatra Sansparshat), air droplet (Ni-shwaasat). This type of the disease is termed as Aupsargika in Ayurveda. Jwar leading to Dhatupaka Awsatha where all three Doshas get vitiated and suppress the Dhatu Bala (immunity) of an individual leading to Oja-Kshaya and ultimately Death. Anupashaya: Vrudha Vaya -Anupashaya. Covid -19 3clpro/ Mpro (PDB ID: 6LU7) structures was obtained from PDB in .pdb format. PDB is an archive for the crystal structures of biological macromolecules, worldwide. The 6LU7 protein contains two chains, A and B, which form a homodimer. Chain A was used for macromolecule preparation. [8] The coronavirus main protease (Mpro), which plays a pivotal role in viral gene expression and replication through the proteolytic processing of replicase polyproteins, is an attractive target for anti CoV drug design. [9] The 160 3-dimensional (3D) structures were obtained from PubChem in .sdf format. PubChem is a chemical substance and biological activities repository consisting of three databases, including substance, compound, and bioassay databases. The compounds used in the present study is shown in table no.2, along with its binding energy with protein. [10] The Ligand was docked against the protein and the interactions were analyzed by using by Drug-like properties were calculated using Lipinski's rule of five, which proposes that molecules with poor permeation and oral absorption have molecular weights > 500, C logP > 5, more than 5 hydrogen-bond donors, and more than 10 acceptor groups. Adherence with Lipinski's rule of five as calculated using SWISS ADME prediction. [12] , [13] , [14] The active site of a protein was determined using the Swiss Target Figure 1 . As though we use phytoconstituents for this study but further research is necessary to investigate the potential uses of the medicinal plants as a whole. Although computer-aided drug design and network pharmacology have been widely used and methodology, we believe that in the future, this methodological process will enable the discovery of new drugs more efficiently, accurately and quickly. This methodology will be more widely usable in future work on revealing and predicting the basis of medicinal materials. Currently, Covid -19 has emerged in the human population and is a potential threat to global health worldwide. Many drug research and developments projects as well as vaccine development research work is in progress. The aim of this study is to examine several medicinal plant-derived compounds that may be used to inhibit the Covid -19 infection pathway. Thus, from the above results obtained from reviewing Ayurveda classics and after the virtual screening of selected drugs we can conclude that Nagaraadi Kashaya may have appreciable results in combating SARS-COV-2. Nagaraadi Kashaya can be a trial candidate for conducting further clinical trial. This paper did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. None. 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