Phytomedicines for Covid-19: Opportunities and Obstacles

COVID-19 is a disease caused by SARS-CoV-2 that can trigger respiratory tract infection. Due to its tendency to affect the upper respiratory tract (sinuses, nose and throat) or lower respiratory tract (windpipe and lungs), this disease is life-threatening and affects a large number of populations. This virus's unique and complex nature enhances the scope to look into the direction of herbal plants and their constituents for its prevention and treatment. The herbal remedies can have preventive as well as therapeutic actions. This review focuses on various aspects of using herbal medicines for COVID-19, as herbal constituents may also have adverse effects. Various studies revealed that some medicinal plants show life-threatening adverse effects, so selecting plants, and their related studies should be appropriate and strategic. This article includes various factors that should be considered before herbal drug use in COVID-19 patients. These are clinical trials, safety, molecular mechanism, and self-medication, which have been elaborated. This article also discusses the targets of covid-19 and different coronavirus strains. As before, treatment diagnosis of the disease is very important. Various patents have been filed and granted for its proper diagnosis so that its treatment can be easy.Copyright © 2022 Society of Pharmaceutical Sciences and Research. All rights reserved.

Jing Si Herbal Drink as a prospective adjunctive therapy for COVID-19 treatment: Molecular evidence and mechanisms

Background: SARS-CoV-2 has led to a sharp increase in the number of hospitalizations and deaths from pneumonia and multiorgan disease worldwide;therefore, SARS-CoV-2 has become a global health problem. Supportive therapies remain the mainstay treatments against COVID-19, such as oxygen inhalation, antiviral drugs, and antibiotics. Traditional Chinese medicine (TCM) has been shown clinically to relieve the symptoms of COVID-19 infection, and TCMs can affect the pathogenesis of SARS-CoV-2 infection in vitro. Jing Si Herbal Drink (JSHD), an eight herb formula jointly developed by Tzu Chi University and Tzu Chi Hospital, has shown potential as an adjuvant treatment for COVID-19 infection. A randomized controlled trial (RCT) of JSHD as an adjuvant treatment in patients with COVID-19 infection is underway Objectives: This article aims to explore the efficacy of the herbs in JSHD against COVID-19 infection from a mechanistic standpoint and provide a reference for the rational utilization of JSHD in the treatment of COVID-19. Method(s): We compiled evidence of the herbs in JSHD to treat COVID-19 in vivo and in vitro. Result(s): We described the efficacy and mechanism of action of the active ingredients in JSHD to treat COVID-19 based on experimental evidence. JSHD includes 5 antiviral herbs, 7 antioxidant herbs, and 7 anti-inflammatory herbs. In addition, 2 herbs inhibit the overactive immune system, 1 herb reduces cell apoptosis, and 1 herb possesses antithrombotic ability. Conclusion(s): Although experimental data have confirmed that the ingredients in JSHD are effective against COVID-19, more rigorously designed studies are required to confirm the efficacy and safety of JSHD as a COVID-19 treatment.Copyright © 2021

Progress on development of vaccines against 2019-nCoV.

Since the outbreak of COVID-19 caused by the 2019-nCoV (SARS-CoV-2), with its high pathogenicity and contagiousness, it has posed a serious threat to global public health security. Up to now, the pathogenesis of 2019-nCoV is unclear, and there is no effective treatment. Vaccine as one of the most effective strategies to prevent virus infection has become a hot area. Based on the current understanding of 2019-nCoV, the development of 2019-nCoV vaccines covers all types: inactivated virus vaccine, recombinant protein vaccine, viral vector-based vaccine, mRNA vaccine, and DNA vaccine, etc. In this review, we focus on the candidate targets of the novel coronavirus, and the types, development status and progress of 2019-nCoV vaccines in order to provide information for further research and prevention.Copyright © 2021 Chinese Medical Association

Molecular Docking Strategy for Multi-Target Inhibitor Discovery of Selected Plant Constituents in Bauhinia Acuminata

Objective: Traditional medicine is often considered to be a kind of complementary or alternative medicine (CAM) nowadays. Therefore, documenting and identifying the herbs that are effective in treating various diseases is vital for future disease control programs. This study aims to perform a molecular docking analysis of the thirteen plant components in Bauhinia acuminata against the target proteins in lung cancer (PDB IDs: 2ITY), breast cancer (1A52), diabetes (3L4U), obesity (IT02), inflammation (5COX) and corona viral infections (6VYO). Material(s) and Method(s): All the plant components used for the present study were retrieved from the plant Bauhinia acuminata and were evaluated for their biological activity results using molinspiration. Further in-silico docking analysis was performed using AutoDock Vina software and the binding interactions were visualized using Discovery studio program. Result and Discussion: The docking scores and analysis of the interactions of the plant components with targets suggest that all the selected plant components showed excellent binding to the chosen targets when compared to that of the standard drugs. As a result of the docking process on 6 different targets, the selected plant components like Quercetin, Beta-sitosterol, and Rheagenine were observed to show good binding energy values against all the 5 targets except 6VYO as shown in (Table 9). These results can further pave the way for getting better insights in identifying and designing potential lead candidates.Copyright © 2022 University of Ankara. All rights reserved.

Therapeutic mechanisms and impact of traditional Chinese medicine on COVID-19 and other influenza diseases

Coronavirus disease 2019 (COVID-19), first reported in Wuhan, China, has rapidly spread worldwide. Traditional Chinese medicine (TCM) has been used to prevent and treat viral epidemics and plagues for over 2,500 years. In the guidelines on fighting against COVID-19, the National Health Commission of the People's Republic of China has recommended certain TCM formulas, namely Jinhua Qinggan granule (JHQGG), Lianhua Qingwen granule (LHQWG), Qingfei Paidu decoction (QFPDD), Xuanfei Baidu granule (XFBD), Xuebijing injection (XBJ), and Huashi Baidu granule (HSBD) for treating COVID-19 infected individuals. Among these six TCM formulas, JHQGG and LHQWG effectively treated mild/moderate and severe COVID-19 infections. XFBD therapy is recommended for mild COVID-19 infections, while XBJ and HSBD effectively treat severe COVID-19 infections. The internationalization of TCM faces many challenges due to the absence of a clinical efficacy evaluation system, insufficient research evidence, and a lack of customer trust across the globe. Therefore, evidence-based research is crucial in battling this infectious disease. This review summarizes SARS-CoV-2 pathogenesis and the history of TCM used to treat various viral epidemics, with a focus on six TCM formulas. Based on the evidence, we also discuss the composition of various TCM formulas, their underlying therapeutic mechanisms, and their role in curing COVID-19 infections. In addition, we evaluated the roles of six TCM formulas in the treatment and prevention of other influenza diseases, such as influenza A (H1N1), severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). Furthermore, we highlighted the efficacy and side effects of single prescriptions used in TCM formulas.Copyright © 2021

Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.

With more than 5 million fatalities and close to 300 million reported cases, COVID-19 is the first documented pandemic due to a coronavirus that continues to be a major health challenge. Despite being rapid, uncontrollable, and highly infectious in its spread, it also created incentives for technology development and redefined public health needs and research agendas to fast-track innovations to be translated. Breakthroughs in computational biology peaked during the pandemic with renewed attention to making all cutting-edge technology deliver agents to combat the disease. The demand to develop effective treatments yielded surprising collaborations from previously segregated fields of science and technology. The long-standing pharmaceutical industry's aversion to repurposing existing drugs due to a lack of exponential financial gain was overrun by the health crisis and pressures created by front-line researchers and providers. Effective vaccine development even at an unprecedented pace took more than a year to develop and commence trials. Now the emergence of variants and waning protections during the booster shots is resulting in breakthrough infections that continue to strain health care systems. As of now, every protein of SARS-CoV-2 has been structurally characterized and related host pathways have been extensively mapped out. The research community has addressed the druggability of a multitude of possible targets. This has been made possible due to existing technology for virtual computer-assisted drug development as well as new tools and technologies such as artificial intelligence to deliver new leads. Here in this article, we are discussing advances in the drug discovery field related to target-based drug discovery and exploring the implications of known target-specific agents on COVID-19 therapeutic management. The current scenario calls for more personalized medicine efforts and stratifying patient populations early on for their need for different combinations of prognosis-specific therapeutics. We intend to highlight target hotspots and their potential agents, with the ultimate goal of using rational design of new therapeutics to not only end this pandemic but also uncover a generalizable platform for use in future pandemics.

The Trimeric Artesunate Analog TF27, a Broadly Acting Anti-Infective Model Drug, Exerts Pronounced Anti-SARS-CoV-2 Activity Spanning Variants and Host Cell Types.

Starting in 2019, the spread of respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated pandemic of the corona virus disease (COVID-19) has led to enormous efforts in the development of medical countermeasures. Although innovative vaccines have scaled back the number of severe COVID cases, the emergence of the omicron variant (B.1.1.529) illustrates how vaccine development struggles to keep pace with viral evolution. On the other hand, while the recently approved antiviral drugs remdesivir, molnupiravir, and Paxlovid are considered as broadly acting anti-coronavirus therapeutics, only molnupiravir and Paxlovid are orally available and none of these drugs are recommended for prophylactic use. Thus, so far unexploited small molecules, targeting strategies, and antiviral mechanisms are urgently needed to address issues in the current pandemic and in putative future outbreaks of newly emerging variants of concern. Recently, we and others have described the anti-infective potential and particularly the pronounced antiviral activity of artesunate and related compounds of the trioxane/sesquiterpene class. In particular, the trimeric derivative TF27 demonstrated strong anti-cytomegalovirus activity at nanomolar concentrations in vitro as well as in vivo efficacy after oral administration in therapeutic and even prophylactic treatment settings. Here, we extended this analysis by evaluating TF27 for its anti-SARS-CoV-2 potential. Our main findings are as follows: (i) compound TF27 exerted strong anti-SARS-CoV-2 activity in vitro (EC50 = 0.46 ± 0.20 µM), (ii) antiviral activity was clearly distinct from the induction of cytotoxicity, (iii) pretreatment with TF27 prevented virus replication in cultured cells, (iv) antiviral activity has likewise been demonstrated in Calu-3 human lung and Caco-2 human colon cells infected with wild-type, delta, or omicron SARS-CoV-2, respectively, and (v) analysis of TF27 combination treatments has revealed synergistic interaction with GC376, but antagonistic interaction with EIDD-1931. Combined, the data demonstrated the pronounced anti-SARS-CoV-2 activity of TF27 and thus highlight the potential of trioxane compounds for further pharmacologic development towards improved options for COVID-specific medication.

The Role of Gut Microbiota on Coronavirus Disease 2019 and Gut Microbiota as Therapeutic Target for COVID-19

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now entered a critical stage worldwide.Patients typically show fever and severe respiratory symptoms, and some others also present gastrointestinal symptoms, like diarrhea, vomiting, nausea, anorexia and also abdominal pain.At present, it is still lack of effective antiviral medicines for this disease, and now clinics mainly focus on symptomatic treatment. The classical theory of traditional Chinese medicine "exterior and interior relationship between lung and large intestine" which coincides with the "gut-lung axis" in modern medicine, this theory indicate alternatives related to gut microbiota might help to control this viral infection. Therefore, this review focus on discusses the relationship between gut microbiota and respiratory viral diseases, the use of probiotics and nutritional therapies to balance the gut microbiota, modulate the immune response and inhibit viral replication. These might be promising alternative pathways in the treatment of COVID-19. Copyright © 2022, Editorial Board of Pharmaceutical Biotechnology. All right reserved.

COVID-19 vaccines: vaccine targets, immunogenicity and allergic reactions

Many vaccine strategies have been developed to control the COVID-19 pandemic. This article presents the mechanisms of action and the efficacy of different vaccines including mRNA- and adenovirus-based vaccines. We will discuss the different vaccine targets, immune responses and allergic reactions which have been reported during the vaccination campaigns. Finally, the latest recommendations for the prevention and management of severe allergic reactions will be summarized. Copyright © 2021 Editions Medecine et Hygiene. All rights reserved.

Machine Learning and Deep Learning Strategies in Drug Repositioning

Drug repositioning invovles exploring novel usages for existing drugs. It plays an important role in drug discovery, especially in the pre-clinical stages. Compared with the traditional drug discovery approaches, computational approaches can save time and reduce cost significantly. Since drug repositioning relies on existing drug-, disease-, and target-centric data, many machine learning (ML) approaches have been proposed to extract useful information from multiple data resources. Deep learning (DL) is a subset of ML and appears in drug repositioning much later than basic ML. Nevertheless, DL methods have shown great performance in predicting potential drugs in many studies. In this article, we review the commonly used basic ML and DL approaches in drug repositioning. Firstly, the related databases are introduced, while all of them are publicly available for researchers. Two types of preprocessing steps, calculating similarities and constructing networks based on those data, are discussed. Secondly, the basic ML and DL strategies are illustrated separately. Thirdly, we review the latest studies focused on the applications of basic ML and DL in identifying potential drugs through three paths: drug-disease associations, drug-drug interactions, and drug-target interactions. Finally, we discuss the limitations in current studies and suggest several directions of future work to address those limitations.

Highlights

Cell Resistance to Ebola and Coronaviruses

Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology.

The need for preparing new strategies for the design of emergency drug therapies against COVID-19 and similar diseases in the future is rather urgent, considering the high rate of morbidity and especially mortality associated with COVID-19, which so far has exceeded 18 million lives. Such strategies could be conceived by targeting the causes and also the serious toxic side effects of the diseases, as well as associated biochemical and physiological pathways. Deferiprone (L1) is an EMA- and FDA-approved drug used worldwide for the treatment of iron overload and also other conditions where there are no effective treatments. The multi-potent effects and high safety record of L1 in iron loaded and non-iron loaded categories of patients suggests that L1 could be developed as a "magic bullet" drug against COVID-19 and diseases of similar symptomatology. The mode of action of L1 includes antiviral, antimicrobial, antioxidant, anti-hypoxic and anti-ferroptotic effects, iron buffering interactions with transferrin, iron mobilizing effects from ferritin, macrophages and other cells involved in the immune response and hyperinflammation, as well as many other therapeutic interventions. Similarly, several pharmacological and other characteristics of L1, including extensive tissue distribution and low cost of production, increase the prospect of worldwide availability, as well as many other therapeutic approach strategies involving drug combinations, adjuvant therapies and disease prevention.

Inhalable Mannosylated Rifampicin-Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy.

Among respiratory infections, tuberculosis was the second deadliest infectious disease in 2020 behind COVID-19. Inhalable nanocarriers offer the possibility of actively targeting anti-tuberculosis drugs to the lungs, especially to alveolar macrophages (cellular reservoirs of the Mycobacterium tuberculosis). Our strategy was based on the development of a mannose-decorated micellar nanoformulation based in Soluplus® to co-encapsulate rifampicin and curcumin. The former is one of the most effective anti-tuberculosis first-line drugs, while curcumin has demonstrated potential anti-mycobacterial properties. Mannose-coated rifampicin (10 mg/mL)-curcumin (5 mg/mL)-loaded polymeric micelles (10% w/v) demonstrated excellent colloidal properties with micellar size ~108 ± 1 nm after freeze-drying, and they remain stable under dilution in simulated interstitial lung fluid. Drug-loaded polymeric micelles were suitable for drug delivery to the deep lung with lung accumulation, according to the in vitro nebulization studies and the in vivo biodistribution assays of radiolabeled (99mTc) polymeric micelles, respectively. Hence, the nanoformulation did not exhibit hemolytic potential. Interestingly, the addition of mannose significantly improved (5.2-fold) the microbicidal efficacy against Mycobacterium tuberculosis H37Rv of the drug-co-loaded systems in comparison with their counterpart mannose-free polymeric micelles. Thus, this novel inhaled nanoformulation has demonstrated its potential for active drug delivery in pulmonary tuberculosis therapy.

Teaching a graduate aourse in pharmaceutical excipients: personal experience and perspectives

Excipients are critically important in converting active pharmaceutical ingredients (API) into drug products that have optimal stability, bioavailability, manufacturability, duration of action, and therapeutic benefits. They will play even greater roles in the future to enable drug targeting, delivery of biotech products and vaccines, gene therapy, continuous manufacturing, 3D printing, and so forth. This commentary describes the author’s experience in teaching a graduate course on excipients at St. John’s University to train students on optimal selection and appropriate use of excipients in formulating dosage forms and development of drug delivery systems. The course is offered in 15 two-hour sessions over a semester, and the course materials are divided into 13 modules on chemistry of different classes of polymeric and non-polymeric excipients and their application in dosage form development, including the use as solubilizing agents, lyophilizing agents, cryoprotectants, buffers, biodegradable materials, and carriers for amorphous solid dispersions and 3D printing. The development of coprocessed excipients, the need for new excipients, and the regulatory aspects of excipients are also covered. The course includes presentations by guest speakers from the industry, and the students also watch virtual presentations from experts that are publicly available from the internet. It is a popular course at St. John’s University taken by all graduate students in the pharmaceutics program. It is recommended that such courses are introduced in other pharmacy schools and academic institutions. The course may be adapted to meet specific needs of different academic programs. Professional associations, such as AAPS and CRS, industry groups like IPEC, and the pharmaceutical industry may be able to help in introducing such courses by providing lecture materials and guest lecturers.

Drug Targeting and Nanomedicine: Lessons Learned from Liver Targeting and Opportunities for Drug Innovation.

Drug targeting and nanomedicine are different strategies for improving the delivery of drugs to their target. Several antibodies, immuno-drug conjugates and nanomedicines are already approved and used in clinics, demonstrating the potential of such approaches, including the recent examples of the DNA- and RNA-based vaccines against COVID-19 infections. Nevertheless, targeting remains a major challenge in drug delivery and different aspects of how these objects are processed at organism and cell level still remain unclear, hampering the further development of efficient targeted drugs. In this review, we compare properties and advantages of smaller targeted drug constructs on the one hand, and larger nanomedicines carrying higher drug payload on the other hand. With examples from ongoing research in our Department and experiences from drug delivery to liver fibrosis, we illustrate opportunities in drug targeting and nanomedicine and current challenges that the field needs to address in order to further improve their success.

The need for a multi-level drug targeting strategy to curb the COVID-19 pandemic.

Thousands of drugs, nutraceuticals and their combinations can be used to select candidate therapeutics for targeting SARS-CoV-2 and its symptoms in order to curb COVID-19. A comprehensive, multi-level strategy against COVID-19 should include drug targeting of biomolecules and biochemical pathways involved in the prevention and proliferation of the infection, and the fatal or serious symptoms following infection. Several drugs are routinely used in the treatment of different categories of seriously ill COVID-19 patients including tocilizumab, remdesivir and dexamethasone. The current risk/benefit assessment supports the emergency testing and approval of more drugs. The process for new drug selection could be based on the identification of one drug for one target, or of a multi-potent drug for many targets and drug combinations for one or more targets, that can cause a substantial reduction in the high mortality rate of COVID-19. Several drugs have been identified that can fit this potential role by targeting different stages of COVID-19 including baricitinib, molnupiravir and PF-07321332/ritonavir and also the combination of deferiprone with N-acetylcysteine for inhibiting the vicious circle of oxidative stress toxicity and endothelial cell damage. Most of these drugs are expected to be effective against all the SARS-CoV-2 variants including Omicron (B.1.1.529) and also the associated COVID-19 complications.