TRADITIONAL TO RECENT APPROACHES IN HERBAL MEDICINE THERAPY OF COVID-19

Coronavirus pneumonia disease (COVID-19) is a newly identified coronavirus strain that causes symptoms ranging from cold-like signs to deaths that reached millions around the world. Until this time, there is no approved vaccine has been invented for clinical use, therefore, developing an effective program for therapy is of high priority to save the lives of patients and protect others from being infected. Nature resembles a huge reservoir of anti-infectious compounds, from which innovative ideas, therapies, and products can be deduced. Chinese herbal medicine had succeeded in the treatment of other coronavirus pneumonia such as SARS, MERS and, H7N9 avian influenza which gives us hope to find the targeted remedy in the traditionally used natural herbs consumed by natives from different regions. This work aims to highlight the use of natural traditional remedies to treat viral pneumonia. This systematic review will include studies of the effects of traditional herbal medicine and its role in the treatment of COVID-19 pneumonia. Although promising results were obtained in many cases, but, only a few studies reported the fractional characterization of bioactive principles and/or mechanisms of action. It is requested that pharmaceutical industries, government agencies, and the scientific community will have a gaze at some of these plants for future research and, to find a potential drug candidates for the development of anti-SARSCoV-2 therapeutics in the near future.                          Peer Review History: Received: 6 September 2020; Revised: 10 October; Accepted: 25 October, Available online: 15 November 2020 Academic Editor: Dr. Sally A. El-Zahaby, Pharos University in Alexandria, Egypt, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 5.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Prof. Dr. Ali Gamal Ahmed Al-kaf, Sana'a university, Yemen, [email protected] Prof. Dr. Amani S. Awaad, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj. KSA. [email protected] Similar Articles: EUCALYPTUS ESSENTIAL OIL; AN OFF-LABEL USE TO PROTECT THE WORLD FROM COVID-19 PANDEMIC: REVIEW-BASED HYPOTHESES THE RISKS AND ADVANTAGES OF ANTI-DIABETES THERAPY IN THE POSITIVE COVID-19 PATIEN

ALIMENTOS, NUTRACÊUTICOS E PLANTAS MEDICINAIS UTILIZADOS COMO PRÁTICA COMPLEMENTAR NO ENFRENTAMENTO DOS SINTOMAS DO CORONAVÍRUS (COVID-19): UMA REVISÃO

The present prospective work of scientific articles related to foods and natural products with anti-Covid activity in databases in order to present a scientific community, to governments and society as main foods, nutraceuticals and medicinal plants as strategies used by countries during the COVID-19 pandemic. A review of articles on food, medicinal plants and biotechnology was carried out in databases of scientific articles such as: CAPES journals, PubMed, Elsevier's Science Direct, Willey on library library, Taylor & Francis Springer-Nature database, BMC, Hindawi, Scielo, ACS - American Chemical Society, Google Scholar, in addition to the Patent Database “The LENS” and “Questel-Orbit”. Foods used in daily life such as garlic, ginger, turmeric, sour orange, vegetables, lactobacilli demonstrate proven anti-virus action. Medicinal plants used by Traditional Chinese, Korean and Indian Medicine also demonstrate anti-Covid activity and used during the coronavirus outbreak. Some medicinal plants, green propolis extract, red propolis extract, royal gelly, polen, honey have also been cited as anti-covid, natural anti-inflammatory and immunomodulatory products.O presente trabalho prospectou artigos científicos relacionadas à alimentos e produtos naturais com atividade anti-Covid com o intuito de apresentar, à comunidade científica, aos governos e à sociedade, dados sobre as principais estratégias nutracêuticas, biotecnológicas e plantas medicinais utilizadas em alguns países durante o enfrentamento da pandemia COVID-19. A revisão de artigos sobre alimentos, plantas medicinais e produtos biotecnológicos foi realizada nas bases de dados periódicos da CAPES, PubMed, Science Direct, Willey on line library, Springer-Nature, Taylor & Francis, BMC, Hindawi, Scielo, ACS – American Chemical Society, Google acadêmico, “The LENS” e Questel-Orbit. Alimentos de uso frequente como alho, gengibre, cúrcuma, laranja azeda, vegetais e lactobacilos demonstraram ação anti-coronavirus comprovada. Foram descritos usos de plantas medicinais da Medicina tradicional Chinesa, Coreana, Indiana bastante utilizadas durante a pandemia. Algumas plantas medicinais e nutracêuticos como: extrato de própolis verde e extrato de própolis vermelha brasileiras, geleia real, pólen e mel também foram citados como produtos anti-covid, antiinflamatórios naturais e imunomodulatórios

Structural basis for the identification of the N-terminal domain of coronavirus nucleocapsid protein as an antiviral target

Coronaviruses (CoVs) cause numerous diseases, including Middle East respiratory syndrome and severe acute respiratory syndrome, generating significant health-related and economic consequences. CoVs encode the nucleocapsid (N) protein, a major structural protein that plays multiple roles in the virus replication cycle and forms a ribonucleoprotein complex with the viral RNA through the N protein's N-terminal domain (N-NTD). Using human CoV-OC43 (HCoV-OC43) as a model for CoV, we present the 3D structure of HCoV-OC43 N-NTD complexed with ribonucleoside 5'-monophosphates to identify a distinct ribonucleotide-binding pocket. By targeting this pocket, we identified and developed a new coronavirus N protein inhibitor, N-(6-oxo-5,6-dihydrophenanthridin-2-yl)(N,N-dimethylamino)acetamide hydrochloride (PJ34), using virtual screening; this inhibitor reduced the N protein's RNA-binding affinity and hindered viral replication. We also determined the crystal structure of the N-NTD-PJ34 complex. On the basis of these findings, we propose guidelines for developing new N protein-based antiviral agents that target CoVs

Lab-on-a-chip for the easy and visual detection of SARS-CoV-2 in saliva based on sensory polymers

The initial stages of the pandemic caused by SARS-CoV-2 showed that early detection of the virus in a simple way is the best tool until the development of vaccines. Many different tests are invasive or need the patient to cough up or even drag a sample of mucus from the throat area. Besides, the manufacturing time has proven insufficient in pandemic conditions since they were out of stock in many countries. Here we show a new method of manufacturing virus sensors and a proof of concept with SARS-CoV-2. We found that a fluorogenic peptide substrate of the main protease of the virus (Mpro) can be covalently immobilized in a polymer, with which a cellulose-based material can be coated. These sensory labels fluoresce with a single saliva sample of a positive COVID-19 patient. The results matched with that of the antigen tests in 22 of 26 studied cases (85% success rate).We gratefully acknowledge the financial support provided by all funders. Author Saul Vallejos coordinates the project leading to these results, which has received funding from "La Caixa" Foundation, under agreement LCF/PR/PR18/51130007. This work was supported by the Regional Government of Castilla y León (Junta de Castilla y León) and by the Ministry of Science and Innovation MICIN and the European Union NextGenerationEU PRTR. Author Jose Miguel García received grant PID2020–113264RB-I00 funded by MCIN/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe”. Ana Arnaiz received funding from Ministerio de Universidades-European Union in the frame of NextGenerationEU RD 289/2021 (Universidad Politécnica de Madrid). Finally, all the authors want to thank the support provided by City Hall of Villadiego “Ayuntamiento de Villadiego” when looking for participants for the proof of concept

Antitarget, Anti-SARS-CoV-2 Leads, Drugs, and the Drug Discovery-Genetics Alliance Perspective

: The most advanced antiviral molecules addressing major SARS-CoV-2 targets (Main protease, Spike protein, and RNA polymerase), compared with proteins of other human pathogenic coronaviruses, may have a short-lasting clinical efficacy. Accumulating knowledge on the mechanisms underlying the target structural basis, its mutational progression, and the related biological significance to virus replication allows envisaging the development of better-targeted therapies in the context of COVID-19 epidemic and future coronavirus outbreaks. The identification of evolutionary patterns based solely on sequence information analysis for those targets can provide meaningful insights into the molecular basis of host-pathogen interactions and adaptation, leading to drug resistance phenomena. Herein, we will explore how the study of observed and predicted mutations may offer valuable suggestions for the application of the so-called "synthetic lethal" strategy to SARS-CoV-2 Main protease and Spike protein. The synergy between genetics evidence and drug discovery may prioritize the development of novel long-lasting antiviral agents

Cell-permeable peptide nucleic acid antisense oligonucleotide platform targeting human betacoronaviruses

IntroductionAntisense oligonucleotides (ASOs) with therapeutic potential have recently been reported to target the SARS-CoV-2 genome. Peptide nucleic acids (PNAs)-based ASOs have been regarded as promising drug candidates, but intracellular delivery has been a significant obstacle. Here, we present novel modified PNAs, termed OPNAs, with excellent cell permeability that disrupt the RNA genome of SARS-CoV-2 and HCoV-OC43 by introducing cationic lipid moiety onto the nucleobase of PNA oligomer backbone.MethodsHCT-8 cells and Caco-2 cells were treated with 1 μM antisense OPNAs at the time of viral challenge and the Viral RNA levels were measured by RT-qPCR three days post infection.ResultsNSP 14 targeting OPNA 5 and 11, reduced the viral titer to a half and OPNA 530, 531 and 533 lowered viral gene expression levels to less than 50% of control by targeting the 5’ UTR region. Several modifications (oligo size and position, etc.) were introduced to enhance the efficacy of selected OPNAs. Improved OPNAs exhibited a dose-dependent reduction in viral replication and nucleoprotein (NP) protein. When a mixture of oligomers was applied to infected cells, viral titer and NP levels decreased by more than eightfold.DiscussionIn this study, we have developed a modified PNA ASO platform with exceptional chemical stability, high binding affinity, and cellular permeability. These findings indicate that OPNAs are a promising platform for the development of antivirals to combat future pandemic viral infections that do not require a carrier

Identification of Potential Ligands of the Main Protease of Coronavirus SARS-CoV-2 (2019-nCoV) Using Multimodal Generative Neural-Networks

The recent outbreak of coronavirus disease 2019 (COVID-19) is posing a global threat to human population. The pandemic caused by novel coronavirus (2019-nCoV), also called as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); first emerged in Wuhan city, Hubei province of China in December 2019. The rapid human to human transmission has caused the contagion to spread world-wide affecting 244,385,444 (244.4 million) people globally causing 4,961,489 (5 million) fatalities dated by 27 October 2021. At present, 6,697,607,393 (6.7 billion) vaccine doses have been administered dated by 27 October 2021, for the prevention of COVID-19 infections. Even so, this critical and threatening situation of pandemic and due to various variants’ emergence, the pandemic control has become challenging; this calls for gigantic efforts to find new potent drug candidates and effective therapeutic approaches against the virulent respiratory disease of COVID-19. In the respiratory morbidities of COVID-19, the functionally crucial drug target for the antiviral treatment could be the main protease/3-chymotrypsin protease (Mpro/3CLpro) enzyme that is primarily involved in viral maturation and replication. In view of this, in the current study I have designed a library of small molecules against the main protease (Mpro) of coronavirus SARS-CoV-2 (2019-nCoV) by using multimodal generative neural-networks. The scaffold-based molecular docking of the series of compounds at the active site of the protein was performed; binding poses of the molecules were evaluated and protein-ligand interaction studies followed by the binding affinity calculations validated the findings. I have identified a number of small promising lead compounds that could serve as potential inhibitors of the main protease (Mpro) enzyme of coronavirus SARS-CoV-2 (2019-nCoV). This study would serve as a step forward in the development of effective antiviral therapeutic agents against the COVID-19