For thousands of years mankind is using plant sources to alleviate or cure illness 1. Novel chemical compounds synthesis from the plant active constituents, which are of potential use in medicine and other usefull application. Herbal remedies are popular remedies for diseases used by a vast vast majority of the world's population 2. Herbal plants having many pharmacologically active compounds like flavonoids, alkaloids, tannin, steroids, glycosides, phenols, fixed oils, which is stored in their specific parts of leaves, bark, flowers, seed, fruits, root etc. 3. Biophytum sensitivum (family-Oxalidaceae) having different pharmacological activities such as dengu,anticancer, antiinflammatory, chemoprotective, antidiabetic and wound healing activities of their different parts 4-8 .

The transdermal drug delivery system is widely accepted due to its numerous advantages as it is a non-invasive drug administration process with prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance, and easy termination of drug therapy. Non-steroidal anti-inflammatory drugs such as Diclofenac sodium, Lornoxicam, Aceclofenac, Ibuprofen, antihypertensive drugs, for example, Repaglinide, Atenolol, and Antiviral agents such as Stavudine, zidovudine represents the most commonly used medications for the treatment of pain and inflammatory reaction but various side effects can limit their use. Therefore, transdermal delivery of these drugs has advantages of avoiding hepatic first-pass effect, gastric irritation and delivering the drug for an extended period of time at a sustained level. The present article mainly focuses on the work been done on these drugs by formulated and delivered as transdermal patches to decrease the side effects related to the oral delivery.

Background The derivatives of quercetin is known for their immune-modulating antiviral, anti-blood clotting, antioxidant, and also for its anti-inflammatory efficacy. The current study was therefore conducted to examine the noted novel derivatives of quercetin present in plant sources as an immune modulator and as an antiviral molecule in the COVID-19 disease and also to study their affinity of binding with potential three targets reported for coronavirus, i.e., papain-like protease, spike protein receptor-binding domain, and 3C-like protease. Based on the high-positive drug-likeness score, the reported derivatives of quercetin obtained from an open-source database were further filtered. Compounds with positive and high drug-likeness scores were further predicted for their potential targets using DIGEP-Pred software, and STRING was used to evaluate the interaction between modulated proteins. The associated pathways were recorded based on the Kyoto Encyclopedia of Genes and Genomes pathway database. Docking was performed finally using PyRx having AutoDock Vina to identify the efficacy of binding between quercetin derivatives with papain-like protease, spike protein receptor-binding domain, and 3C-like protease. The ligand that scored minimum binding energy was chosen to visualize the interaction between protein and ligand. Normal mode analysis in internal coordinates was done with normal mode analysis to evaluate the physical movement and stability of the best protein-ligand complexes using the iMODS server. Results Forty bioactive compounds with the highest positive drug-likeness scores were identified. These 40 bioactives were responsible for regulating different pathways associated with antiviral activity and modulation of immunity. Finally, three lead molecules were identified based on the molecular docking and dynamics simulation studies with the highest anti-COVID-19 and immunomodulatory potentials. Standard antiviral drug remdesivir on docking showed a binding affinity of − 5.8 kcal/mol with PLpro, − 6.4 kcal/mol with 3CLpro, and − 8.6 kcal/mol with spike protein receptor-binding domain of SARS-CoV-2, the discovered hit molecules quercetin 3-O-arabinoside 7-O-rhamnoside showed binding affinity of − 8.2 kcal/mol with PLpro, whereas quercetin 3-[rhamnosyl-(1- > 2)-alpha-L-arabinopyranoside] and quercetin-3-neohesperidoside-7-rhamnoside was predicted to have a binding affinity of − 8.5 kcal/mol and − 8.8 kcal/mol with spike protein receptor-binding domain and 3CLpro respectively Conclusion Docking study revealed quercetin 3-O-arabinoside 7-O-rhamnoside to possess the highest binding affinity with papain-like protease, quercetin 3-[rhamnosyl-(1- > 2)-alpha-L-arabinopyranoside] with spike protein receptor-binding domain, and quercetin-3-neohesperidoside-7-rhamnoside with 3C-like protease and all the protein-ligand complexes were found to be stable after performing the normal mode analysis of the complexes in internal coordinates. Graphical Abstract

The pandemic, which is brought about by the SARS CoV-2 infection, has inundated the entire world and obliterated the economies of numerous nations. Hence, looking for treatment and prophylaxis of COVID-19, Quercetin, which is a flavonoid gotten from plants and different sources like grapes, onion, tomatoes, apple, and so forth and has various properties like calming property, cardioprotective, and neuroprotective properties, is inspected for its antiviral properties, so it tends to be considered as one of the adjuvant medicines alongside the pharmacological medicines like Remdesivir and plasma treatment. A survey of the antiviral property of Quercetin from distributed articles proposes that Quercetin has a solid antiviral movement towards SARS C0V-2 and other upper respiratory tract infections. It can be securely and financially used to battle COVID-19. For high-hazard populaces, this medication can be a brilliant decision of treatment. Here the authors give proof to the utilization of Quercetin in relationship with pharmacological treatments like Remdesivir or improving plasma treatment.

Antioxidants are substances that can prevent cells from the damage caused by unstable molecules such as free radicals. Quercetin, a plant pigment present in many fruits, vegetables, grains, and one of the most beneficial antioxidants in the diet and plays an important role in helping the body and prevent free radical damage, which is linked to chronic diseases. The antioxidant properties of quercetin may help to reduce inflammation, allergy symptoms, blood pressure. A lot of studies have been done and experiments have been conducted both in vivo and in vitro and it has been found that in cultured cells many respiratory viruses were inhibited by quercetin. At a minimal inhibitory concentration of 0.03 to 0.5μg/ml in WI-38 or Hela cells, Cytopathic effects produced by echovirus type 7,11,12,19, rhinovirus, poliovirus, and coxsackievirus A21 and B1 were inhibited. The plaque formed by DNA and RNA viruses such as Herpes Simplex Virus-1, Polio type 1, and parainfluenza types 3 were effectively reduced demonstrating its anti-replicative properties. This article reviews effect of quercetin on different types of viral infections.