Research progress on the regulation of endothelial cells by natural products of traditional Chinese medicine in the prevention and treatment of atherosclerosis

[] Atherosclerosis (As) is the pathological basis of coronary heart disease, and vascular endothelial injury is the initiating factor of coronary atherosclerosis. Vascular endothelial cells are a single layer of cells located in the inner layer of blood vessels and regulates exchanges between the blood stream and the surrounding tissues, and their integrity is very important. Many active monomers and the derivatives in natural products of traditional Chinese medicine modulate the function of endothelial cells by intervening oxidative stress, regulating the release of vasoactive substances, reducing inflammation, and equilibrating coagulation and anticoagulant system. They have the advantages of multi-pathway, multi-link and multi-target regulation in protecting from endothelial injury and attenuating atherogenesis. They have also been used to protect against corona virus disease 2019 (COVID-19) induced endothelial injury and atheroslerosis. This article reviews the research progress of the above issues in this field. © 2023, Editorial Office of Chinese Journal of Arteriosclerosis. All rights reserved.

Antibacterial and Antiviral Activities of Microwave-assisted Thuja orientalis Extracts

In this study, the components of microwave-assisted extracts obtained from Thuja orientalis leaves were analyzed, and the cytotoxicity, antibacterial and antiviral activities were evaluated. The predominant components from microwave-assisted extraction were catechin, leucopelargonidin, arecatannin, quinolone, and kaempferol derivatives, which are classified in the fla-vonoid and tannin groups. We observed that the 0.11 mg/mL of extract concentration did not show cytotoxicity in HaCaT cells. The antibacterial activities were tested according to the guidelines of methods for determining the bactericidal activity of antimicrobial agents. The extracts showed 99.9% antibacterial efficiency against gram-positive S. aureus, while the anti-bacterial effect on gram-negative E. coli was insignificant. When the extract concentration and contact time with bacteria were increased, 99.9% antibacterial efficiency was observed for E. coli as well as S. aureus. Following the standard to assess the activity of microbicides against viruses in suspension (ASTM-E1052-20), the antiviral efficiency was more than 99.99% for influenza A (H1N1) and SARS-CoV-2. These results suggest its potential use in antiviral disinfectants, surface coatings, personal protective equipment, and textiles. © 2023 The Korean Society of Industrial and Engineering Chemistry. All rights reserved.

Structure-based virtual identification of natural inhibitors of SARS-CoV-2 and its Delta and Omicron variant proteins

Plain language summaryMutant strains of SARS-CoV-2 called 'variants of concern' (VOCs) are linked to a good ability to infect, re-infect and spread among people. They are also linked to poor ability to fight the disease and reduced effectiveness of vaccines. Delta and Omicron are important VOCs because they are difficult to control and treat. Specific resistance to some drugs used to treat COVID-19 poses a further challenge. Therefore, discovering natural or plant-derived drugs with no known resistance would be valuable to the treatment of COVID-19. In this study, we screen and identify seven plant-derived compounds that may be useful to treating COVID-19 - we identify Quercetin-3-acetyl-glucoside, Rutin, Kaempferol, Catechin, Orientin, Obetrioside and Neridienone A as potential candidates. Orientin, Obetrioside, Catechin and Neridienone A are identified as candidates against Delta and Omicron for the first time. Aim: Structure-based identification of natural compounds against SARS-CoV-2, Delta and Omicron target proteins. Materials & methods: Several known antiviral natural compounds were subjected to molecular docking and MD simulation against SARS-CoV-2 Mpro, Helicase and Spike, including Delta and Omicron Spikes. Results: Of the docked ligands, 20 selected for each complex exhibited overall good binding affinities (-7.79 to -5.06 kcal/mol) with acceptable physiochemistry following Lipinski's rule. Finally, two best ligands from each complex upon simulation showed structural stability and compactness. Conclusion: Quercetin-3-acetyl-glucoside, Rutin, Kaempferol, Catechin, Orientin, Obetrioside and Neridienone A were identified as potential inhibitors of SARS-CoV-2 Mpro, Helicase and Spike, while Orientin and Obetrioside also showed good binding-affinities with Omicron Spike. Catechin and Neridienone A formed stable complexes with Delta Spike. Tweetable We report structure-based identification of natural compounds viz., Quercetin-3-acetyl-glucoside, Rutin, Kaempferol, Catechin, Orientin, Obetrioside and Neridienone A against SARS-CoV-2 Mpro, Helicase and Spike as well as Delta and Omicron Spike proteins.

4th International Conference on Natural Resources and Technology, Sumatera Utara, Indonesia, 29-30 August 2022

These proceedings, with a theme of Natural Resources and Technology for Achieving Sustainable Development Goal through Academic, Industry, and Community and a subtheme of Resilience and Innovation Research on Sustainable Natural Resources and Technology Post-Covid 19, contain 104 articles covering 6 major topics in the related fields such as (i) Natural science and natural product, (ii) Natural resource technology, (iii) Information systems of tropical resources, (iv) Tropical biodiversity, (v) Food science and food technology, and (vi) Ethnobotany and ethnozoology.

Broad-Spectrum Antivirals Derived from Natural Products.

Scientific advances have led to the development and production of numerous vaccines and antiviral drugs, but viruses, including re-emerging and emerging viruses, such as SARS-CoV-2, remain a major threat to human health. Many antiviral agents are rarely used in clinical treatment, however, because of their inefficacy and resistance. The toxicity of natural products may be lower, and some natural products have multiple targets, which means less resistance. Therefore, natural products may be an effective means to solve virus infection in the future. New techniques and ideas are currently being developed for the design and screening of antiviral drugs thanks to recent revelations about virus replication mechanisms and the advancement of molecular docking technology. This review will summarize recently discovered antiviral drugs, mechanisms of action, and screening and design strategies for novel antiviral agents.

Inhibitory effects of 190 compounds against SARS-CoV-2 Mpr o protein: Molecular docking interactions.

COVID-19 has caused many deaths since the first outbreak in 2019. The burden on healthcare systems around the world has been reduced by the success of vaccines. However, population adherence and the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are still challenging tasks to be affronted. In addition, the newly approved drug presents some limitations in terms of side effects and drug interference, highlighting the importance of searching for new antiviral agents against SARS-CoV-2. The SARS-CoV-2 main protease (Mpr o ) represents a versatile target to search for new drug candidates due to its essential role in proteolytic activities responsible for the virus replication. In this work, a series of 190 compounds, composed of 27 natural ones and 163 synthetic compounds, were screened in vitro for their inhibitory effects against SARS-CoV-2 Mpro . Twenty-five compounds inhibited Mpro with inhibitory constant values (Ki ) between 23.2 and 241 µM. Among them, a thiosemicarbazone derivative was the most active compound. Molecular docking studies using Protein Data Bank ID 5RG1, 5RG2, and 5RG3 crystal structures of Mpro revealed important interactions identified as hydrophobic, hydrogen bonding and steric interactions with amino acid residues in the active site cavity. Overall, our findings indicate the described thiosemicarbazones as good candidates to be further explored to develop antiviral leads against SARS-CoV-2. Moreover, the studies showed the importance of careful evaluation of test results to detect and exclude false-positive findings.

COVID-19 Therapeutic Potential of Natural Products.

Despite the fact that coronavirus disease 2019 (COVID-19) treatment and management are now considerably regulated, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component), have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Their abundant resources and excellent antiviral performance make natural products a relatively cheap and readily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.

New progresses on cell surface protein HSPA5/BiP/GRP78 in cancers and COVID-19.

Heat-shock-protein family A (Hsp70) member 5 (HSPA5), aliases GRP78 or BiP, is a protein encoded with 654 amino acids by the HSPA5 gene located on human chromosome 9q33.3. When the endoplasmic reticulum (ER) was stressed, HSPA5 translocated to the cell surface, the mitochondria, and the nucleus complexed with other proteins to execute its functions. On the cell surface, HSPA5/BiP/GRP78 can play diverse functional roles in cell viability, proliferation, apoptosis, attachments, and innate and adaptive immunity regulations, which lead to various diseases, including cancers and coronavirus disease 2019 (COVID-19). COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which caused the pandemic since the first outbreak in late December 2019. HSPA5, highly expressed in the malignant tumors, likely plays a critical role in SARS-CoV-2 invasion/attack in cancer patients via tumor tissues. In the current study, we review the newest research progresses on cell surface protein HSPA5 expressions, functions, and mechanisms for cancers and SARS-CoV-2 invasion. The therapeutic and prognostic significances and prospects in cancers and COVID-19 disease by targeting HSPA5 are also discussed. Targeting HSPA5 expression by natural products may imply the significance in clinical for both anti-COVID-19 and anti-cancers in the future.

Natural Product-Based Screening for Lead Compounds Targeting SARS CoV-2 Mpro.

Drugs that cure COVID-19 have been marketed; however, this disease continues to ravage the world without becoming extinct, and thus, drug discoveries are still relevant. Since Mpro has known advantages as a drug target, such as the conserved nature of the active site and the absence of homologous proteins in the body, it receives the attention of many researchers. Meanwhile, the role of traditional Chinese medicine (TCM) in the control of epidemics in China has also led to a focus on natural products, with the hope of finding some promising lead molecules through screening. In this study, we selected a commercial library of 2526 natural products from plants, animals and microorganisms with known biological activity for drug discovery, which had previously been reported for compound screening of the SARS CoV-2 S protein, but had not been tested on Mpro. This library contains compounds from a variety of Chinese herbs, including Lonicerae Japonicae Flos, Forsythiae Fructus and Scutellariae Radix, which are derived from traditional Chinese medicine prescriptions that have been shown to be effective against COVID-19. We used the conventional FRET method for the initial screening. After two rounds of selection, the remaining 86 compounds were divided into flavonoids, lipids, phenylpropanoids, phenols, quinones, alkaloids, terpenoids and steroids according to the skeleton structures, with inhibition rates greater than 70%. The top compounds in each group were selected to test the effective concentration ranges; the IC50 values were as follows: (-)-gallocatechin gallate (1.522 ± 0.126 µM), ginkgolic acid C15:1 (9.352 ± 0.531 µM), hematoxylin (1.025 ± 0.042 µM), fraxetin (2.486 ± 0.178 µM), wedelolactone (1.003 ± 0.238 µM), hydroxytyrosol acetate (3.850 ± 0.576 µM), vanitiolide (2.837 ± 0.225 µM), ß,ß-dimethylacrylalkannin (2.731 ± 0.308 µM), melanin (7.373 ± 0.368 µM) and cholesteryl sodium sulfate (2.741 ± 0.234µM). In the next step, we employed two biophysical techniques, SPR and nanoDSF, to obtain KD/Kobs values: hematoxylin (0.7 µM), (-)-gallocatechin gallate (126 µM), ginkgolic acid C15:1 (227 µM), wedelolactone (0.9770 µM), ß,ß-dimethylacrylalkannin (1.9004 µM,), cholesteryl sodium sulfate (7.5950 µM) and melanin (11.5667 µM), which allowed better assessments of the binding levels. Here, seven compounds were the winners. Then, molecular docking experiments were specially performed by AutoDock Vina to analyze the mode of interactions within Mpro and ligands. We finally formulated the present in silico study to predict pharmacokinetic parameters as well as drug-like properties, which is presumably the step that tells humans whether the compounds are drug-like or not. Moreover, hematoxylin, melanin, wedelolactone, ß,ß-dimethylacrylalkannin and cholesteryl sodium sulfate are in full compliance with the "Lipinski" principle and possess reasonable ADME/T properties, they have a greater potential of being lead compounds. The proposed five compounds are also the first to be found to have potential inhibitory effects on SARS CoV-2 Mpro. We hope that the results in this manuscript may serve as benchmarks for the above potentials.

Anticoagulant effect of Feijoa sellowiana extracts generated by different biotechnological techniques.

Blood clotting has become one of the most dangerous side effects associated with Corona virus, as well as the high level of cholesterol and triglycerides in the blood. Therefore, it has become necessary to use medicinal plants that are biologically safe and containing anti-clotting compound. Feijoa sellowiana represents a prolific source diverse compounds that may have thrombolytic activity. Therefore, the main research point is the production and scaling up of a target contents that have anticoagulants by using biotechnological techniques; calli production, and bioreactors and assessed their activity through in-vivo study. Murashige and Skoog (MS) medium enriched with varying concentrations of benzyl adenine (BA) and naphthalene acetic acid (NAA) was used to cultivate calli and cell suspension cultures from F. sellowiana seeds. Bioreactors were employed to boost active constituent's production. Moreover, the bioreactor physical factors such as effect of controlled or uncontrolled pH medium were investigated. The leaves of the main plant were extracted by ethanol 70% and polar and non-polar extracts were also prepared. The ethanol extract of calli and cells resulting from bioreactors were also prepared. All prepared extracts were subjected to chemical analysis by HPLC, in-vitro antioxidant assays, in-vivo anticoagulant activity and histopathological examination. Calli and cell suspension cultures were produced by using MS medium fortified with 1 mg/L BA+ 0.1 mg/L NAA. It was found that culturing of cell cultures in a bioreactor with uncontrolled pH and aeration at the value of 0.5 L/min gave the maximum and economical fresh and dry weights of the plants. After evaluation of all extracts; it was found that the calli ethanol extract for each plant was the highest value of total phenolic and total flavonoid contents either quantitatively or qualitatively. All extracts of Feijoa had antioxidant activity. The IC50 of the DPPH of Feijoa calli extract was 13.45 µg/mL, it was also confirmed by FRAP and ABTs values. Feijoa calli extract decreased platelet aggregation by suppression of thrombin, extended aPTT, PT, bleeding and clotting times. It was safer than warfarin medication. From these findings the authors can conclude that Feijoa had highly anticoagulant activity and the calli production achieved the goal of the enhancement of the phenolic constituent and thus their activity.

Role of Natural Products in the Management of COVID-19: A Saudi Arabian Perspective.

The coronavirus disease of 2019 (COVID-19) pandemic has resulted in an unprecedented circumstance that has never previously occurred. This has caused the Saudi Arabian people to recognize the necessity of preventive measures and explore alternative systems, such as using natural products (NPs), for treating their infection. Therefore, the specific objectives of this study were to explore the factors that influence the selection of NPs for COVID-19 management and to know the outcome of using NPs in COVID-19 infection management. This observational cross-sectional study was conducted in Saudi Arabia between February and April 2022. The validated pretested questionnaire was distributed among different regions of the country via a purposive snowball sampling procedure. Both descriptive statistics and stepwise regression analyses were carried out to evaluate the parameters related to the use of medicinal plants for the prevention of COVID-19 and the treatment of respiratory symptoms during the pandemic. The data obtained were statistically analyzed using IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, NY, USA). Of the 677 participants, 65% reported using NPs for themselves or family members during COVID-19. Utilizing NPs is always given priority by a significant (p < 0.001) percentage of survey respondents. Further, a highly significant (p < 0.001) percentage of participants felt that using NPs reduced their COVID-19 symptoms without having any remarkable (p < 0.001) adverse effects. Family and friends (59%) were the most frequent sources of information about utilizing NPs, followed by personal experience (41%). Honey (62.7%) and ginger (53.8%) were the most utilized NP among participants. Moreover, black seeds, garlic and turmeric were used by 40.5%, 37.7% and 26.3% of the surveyors, respectively. Those who used NPs before COVID-19 were 72.9% more likely to use them during COVID-19. NPs are more likely to be used by 75% of people who live in the central part of the country and whose families prefer it. This is true even if other factors are considered, such as the practice of using NPs along with traditional therapies and the fact that some participants' families prefer it. Our findings show that NPs were commonly used to treat COVID-19 infection among Saudi Arabian residents. Close friends and family members mainly encouraged the use of NPs. Overall, the use of NPs was high among those who participated in our study; such practices are strongly impacted by society. It is essential to promote extensive studies to improve the recognition and accessibility of these products. Authorities should also educate the people about the benefits and risks of using commonly used NPs, especially those reported in this study.

Antibacterial and Antiviral Activities of Microwave-assisted Thuja orientalis Extracts

In this study, the components of microwave-assisted extracts obtained from Thuja orientalis leaves were analyzed, and the cytotoxicity, antibacterial and antiviral activities were evaluated. The predominant components from microwave-assisted extraction were catechin, leucopelargonidin, arecatannin, quinolone, and kaempferol derivatives, which are classified in the fla-vonoid and tannin groups. We observed that the 0.11 mg/mL of extract concentration did not show cytotoxicity in HaCaT cells. The antibacterial activities were tested according to the guidelines of methods for determining the bactericidal activity of antimicrobial agents. The extracts showed 99.9% antibacterial efficiency against gram-positive S. aureus, while the anti-bacterial effect on gram-negative E. coli was insignificant. When the extract concentration and contact time with bacteria were increased, 99.9% antibacterial efficiency was observed for E. coli as well as S. aureus. Following the standard to assess the activity of microbicides against viruses in suspension (ASTM-E1052-20), the antiviral efficiency was more than 99.99% for influenza A (H1N1) and SARS-CoV-2. These results suggest its potential use in antiviral disinfectants, surface coatings, personal protective equipment, and textiles. © 2023 The Korean Society of Industrial and Engineering Chemistry. All rights reserved.

In-silico screening of plant-derived natural compounds for their anti-COVID-19 potential

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019 and quickly spread across the worldwide. It becomes a global pandemic and risk to the healthcare system of almost every nation around the world. In this study thirty natural compounds of 19 Indian herbal plants were used to analyze their binding with eight proteins associated with COVID -19. Based on the molecular docking as well as ADMET analysis, isovitexin, glycyrrhizin, sitosterol, and piperine were identified as potential herbal medicine candidates. On comparing the binding affinity with Ivermectin, we have found that the inhibition potentials of the Trigonella foenum-graecum (fenugreek), Glycyrrhiza glabra (licorice), Tinospora cordifolia (giloy) and Piper nigrum (black pepper) are very promising with no side-effects.

Molecular modeling study of natural products as potential bioactive compounds against SARS-CoV-2.

CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 infection and responsible for millions of victims worldwide, remains a significant threat to public health. Even after the development of vaccines, research interest in the emergence of new variants is still prominent. Currently, the focus is on the search for effective and safe drugs, given the limitations and side effects observed for the synthetic drugs administered so far. In this sense, bioactive natural products that are widely used in the pharmaceutical industry due to their effectiveness and low toxicity have emerged as potential options in the search for safe drugs against COVID-19. Following this line, we screened 10 bioactive compounds derived from cholesterol for molecules capable of interacting with the receptor-binding domain (RBD) of the spike protein from SARS-CoV-2 (SC2Spike), responsible for the virus's invasion of human cells. Rounds of docking followed by molecular dynamics simulations and binding energy calculations enabled the selection of three compounds worth being experimentally evaluated against SARS-CoV-2. METHODS: The 3D structures of the cholesterol derivatives were prepared and optimized using the Spartan 08 software with the semi-empirical method PM3. They were then exported to the Molegro Virtual Docking (MVD®) software, where they were docked onto the RBD of a 3D structure of the SC2Spike protein that was imported from the Protein Data Bank (PDB). The best poses obtained from MVD® were subjected to rounds of molecular dynamics simulations using the GROMACS software, with the OPLS/AA force field. Frames from the MD simulation trajectories were used to calculate the ligand's free binding energies using the molecular mechanics - Poisson-Boltzmann surface area (MM-PBSA) method. All results were analyzed using the xmgrace and Visual Molecular Dynamics (VMD) software.

An overview on medicinal plants used for combating coronavirus: Current potentials and challenges.

Worldwide, Severe acute respiratory syndrome Coronavirus (SARS-CoV-2) pandemic crisis, causing many morbidities, mortality, and devastating impact on economies, so the current outbreak of the CoV-2 is a major concern for global health. The infection spread quickly and caused chaos in many countries around the world. The slow discovery of CoV-2 and the limited treatment options are among the main challenges. Therefore, the development of a drug that is safe and effective against CoV-2 is urgently needed. The present overview briefly summarizes CoV-2 drug targets ex: RNA-dependent RNA polymerase (RdRp), papain-like protease (PLpro), 3-chymotrypsin-like protease (3CLpro), transmembrane serine protease enzymes (TMPRSS2), angiotensin-converting enzyme 2 (ACE2), structural protein (N, S, E, and M), and virulence factors (NSP1, ORF7a, and NSP3c) for which drug design perspective can be considered. In addition, summarize all anti-COVID-19 medicinal plants and phytocompounds and their mechanisms of action to be used as a guide for further studies.

A Multi-dimensional Review on Severe Acute Respiratory Syndrome CoronaVirus-2.

The advent and spread of novel coronavirus viruses (nCoV), has been presenting the planet with a new public health crisis since December 2019. Several cases of unexplained pneumonia occurred in Wuhan, Hubei Province, China, only a month before the Chinese Spring festival. After a diagnosis of broncho-alveolar fluid samples of people from the Wuhan Seafood Market, the new coronavirus was identified using next-generation sequence technology. This work aims to bring out information regarding COVID-19 under a common platform that will help the researchers to identify the vital therapeutic targets for SARS-CoV-2 and, also it will provide insights into some significant work performed in recent times by scientific communities around the globe. In this review, we have tried to explore multiple aspects related to COVID-19 that includes: Epidemiology, Etiology, COVID-19 variants, Vaccine candidates, Potential therapeutic targets, role of natural products, and computational studies in drug design and development, repurposing, analysis of crystal structures available for COVID-19 related protein structures. Druggable targets include all viral enzymes and proteins involved in viral replication and regulation of host cellular machines. The medical community is tracking several therapies to combat the infection by using various antiviral and immunomodulatory mechanisms. While some vaccines are approved in this world-wide health crisis, a more precise therapy or drug is formally recommended to be used against SARS-CoV-2 infection. Natural products other than synthetic drugs, have been tested by in silico analysis against COVID-19. However, important issues still need to be addressed regarding in vivo bioavailability and better efficacy.

Drug–Target Interaction Deep Learning-Based Model Identifies the Flavonoid Troxerutin as a Candidate TRPV1 Antagonist

Based on the advances made by artificial intelligence (AI) technologies in drug discovery, including target identification, hit molecule identification, and lead optimization, this study investigated natural compounds that could act as transient receptor potential vanilloid 1 (TRPV1) channel protein antagonists. Using a molecular transformer drug–target interaction (MT-DTI) model, troxerutin was predicted to be a TRPV1 antagonist at IC50 582.73 nM. In a TRPV1-overexpressing HEK293T cell line, we found that troxerutin antagonized the calcium influx induced by the TRPV1 agonist capsaicin in vitro. A structural modeling and docking experiment of troxerutin and human TRPV1 confirmed that troxerutin could be a TRPV1 antagonist. A small-scale clinical trial consisting of 29 participants was performed to examine the efficacy of troxerutin in humans. Compared to a vehicle lotion, both 1% and 10% w/v troxerutin lotions reduced skin irritation, as measured by skin redness induced by capsaicin, suggesting that troxerutin could ameliorate skin sensitivity in clinical practice. We concluded that troxerutin is a potential TRPV1 antagonist based on the deep learning MT-DTI model prediction. The present study provides a useful reference for target-based drug discovery using AI technology and may provide useful information for the integrated research field of AI technology and biology.

Natural antimicrobials: An introduction

From historical point of view, nature has always been a rich source of materials, and medicines also came from this vast and immeasurable resource. Ethnologically-based information still has great potential for future explanations of bioactivities of such medicines. Although epidemiological measures (vaccinations) and antimicrobial treatments curb infectious diseases, there is still an urgent need for well-defined molecules from nature. With the decline of de novo synthesis of new chemical entities, the main focus of nature-derived molecule research among the group of antimicrobials is clear definition of antimicrobial spectrum of activities, mechanism of action, stability, mutagenicity and genotoxicity. The possible road is also in silico studies of antimicrobial activities of natural molecules from natural products databases. Cleary displayed preclinical studies may lead to the in vivo studies which can prove the indication of such natural molecules. The main obstacles such as low bioavailability, short half-life and low PK/PD values will be a great challenge for future research. Considering the emerging new diseases, such as SARS-CoV-2 nowadays, and rising scientific awareness about testing known natural molecules, the area of natural antimicrobials is fast, prominent and still encouraging. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2022. All rights reserved.

Computational studies on the design of NCI natural products as inhibitors to SARS-CoV-2 main protease.

The pandemic coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 5 million deaths globally. Currently there are no effective drugs available to treat COVID-19. The viral protease replication can be blocked by the inhibition of main protease that is encoded in polyprotein 1a and is therefore a potential protein target for drug discovery. We have carried out virtual screening of NCI natural compounds followed by molecular docking in order to identify hit molecules as probable SARS-CoV-2 main protease inhibitors. The molecular dynamics (MD) simulations of apo form in complex with N3, α-ketoamide and NCI natural products was used to validate the screened compounds. The MD simulations trajectories were analyzed using normal mode analysis and principal component analysis revealing dynamical nature of the protein. These findings aid in understanding the binding of natural products and molecular mechanisms of SARS-CoV-2 main protease inhibition.Communicated by Ramaswamy H. Sarma.