Antiviral effects of phytochemicals against severe acute respiratory syndrome coronavirus 2 and their mechanisms of action: A review.

The worldwide spreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to health, economic, environmental, and social aspects of human lives. Currently, there are no approved treatments that can effectively block the virus although several existing antimalarial and antiviral agents have been repurposed and allowed use during the pandemic under the emergency use authorization (EUA) status. This review gives an updated overview of the antiviral effects of phytochemicals including alkaloids, flavonoids, and terpenoids against the COVID-19 virus and their mechanisms of action. Search for natural lead molecules against SARS-CoV-2 has been focusing on virtual screening and in vitro studies on phytochemicals that have shown great promise against other coronaviruses such as SARS-CoV. Until now, there is limited data on in vivo investigations to examine the antiviral activity of plants in SARS-CoV-2-infected animal models and the studies were performed using crude extracts. Further experimental and preclinical investigations on the in vivo effects of phytochemicals have to be performed to provide sufficient efficacy and safety data before clinical studies can be performed to develop them into COVID-19 drugs. Phytochemicals are potential sources of new chemical leads for the development of safe and potent anti-SARS-CoV-2 agents.

Use of hydroxychloroquine and azithromycin combination to treat the COVID-19 infection.

Coronavirus disease 2019 (COVID-19) infection is unequivocally the worst crisis in recent decades, which is caused by a severe acute respiratory virus 2. Currently, there is no effective therapy for the COVID-19 infection. Different countries have different guidelines for treating COVID-19 in the absence of an approved therapy for COVID-19. Therefore, there is an imminent need to identify effective treatments, and several clinical trials have been conducted worldwide. Both hydroxychloroquine [HCQS], chloroquine, and azithromycin (AZ) have been widely used for management based on in vitro studies favoring antiviral effects against the COVID-19 virus. However, there is evidence both in favor and against the use of hydroxychloroquine and azithromycin (HCQS+AZ) combination therapy to manage the COVID-19 infection. The combination of hydroxychloroquine and azithromycin was significantly associated with increased adverse events. However, the inference of these findings was from observational studies. Therefore, large randomized trials are imperative to show the future path for the use of HCQS+AZ combination therapy. However, owing to the ban on HCQS use in COVID-19, this may no longer be essential. This review is on the pharmacology, trials, regimens, and side effects of hydroxychloroquine and azithromycin combination therapy.

Identification of a Synthetic Polyhydroxyphenolic Resveratrol Analogue, 3,3',4,4',5,5'-Hexahydroxy-trans-Stilbene with Anti-SARS-CoV-2 Activity.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has been causing the COVID-19 pandemic since December 2019, with over 600 million infected persons worldwide and over six million deaths. We investigated the anti-viral effects of polyphenolic green tea ingredients and the synthetic resveratrol analogue 3,3',4,4',5,5'-hexahydroxy-trans-stilbene (HHS), a compound with antioxidant, antitumor and anti-HIV properties. In the TCID50 assay, four out of nine green tea constituents showed minor to modest cell protective effects, whereas HHS demonstrated the highest reduction (1103-fold) of the TCID50, indicating pronounced inhibition of virus replication. HHS was also a highly effective inhibitor of SARS-CoV-2 proliferation in VeroE6 cells with an IC50 value of 31.1 µM. HSS also inhibited the binding of the receptor-binding domain (RBD) of the spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor (RBD-ACE2) binding with 29% at 100 µM and with 9.2% at 50 µM indicating that the SARS-CoV-2 inhibitory effect might at least in part be attributed to the inhibition of virus binding to ACE2. Based on the chemical similarity to other polyphenols, the oral bioavailability of HHS is likely also very low, resulting in blood levels far below the inhibitory concentration of EGCG against SARS-CoV-2 observed in vitro. However, administration of HHS topically as a nose or throat spray would increase concentrations several-fold above the minimal inhibitory concentration (MIC) in the mucosa and might reduce virus load when administered soon after infection. Due to these promising tissue culture results, further preclinical and clinical studies are warranted to develop HHS as an additional treatment option for SARS-CoV-2 infection to complement vaccines, which is and will be the main pillar to combat the COVID-19 pandemic.

Impact of supplemental vitamins and natural honey for treatment of COVID-19: A review

Abstract The main aim of the paper is to assess whether vitamin C, vitamin D, and natural honey can be administered in the course of the COVID-19 pandemic for promising in line methods with recent evidence. Both systematic literature and clinical trial identification were conducted by searching various databases. A total 58 articles and 29 clinical trials were selected wherein 11 for vitamin C, 16 for vitamin D, and 2 for natural honey were identified for analysis. The high doses of vitamin C (i.e. '200 mg/kg body weight/day, divided into 4 doses') has been found to reduce COVID-19 lung damage, various flu infections. Additionally, the high doses of vitamin C can shorten around 7.8% stay in the intensive care unit. At the same time, vitamin D can effectively protect from lung injury and acute respiratory infections whereas vitamin D deficiency severely affects 75% of the institutionalized people (serum 25(OH) D < 25 nmol/L). Meanwhile, natural honey which contains proteins (0.1-0.4%); ash (0.2%); water (15-17%) has potential antiviral effects and the ability to improve immunity. Therefore, the administration of vitamins and honey is the promising evidence-based approach for reducing fatalities, saving lives, and bringing the COVID-19 pandemic to a rapid end. It is believed that the utilization of vitamin C, vitamin D, and natural honey with the current treatment may be effective in treating COVID-19-caused fatal complications such as pneumonia. Therefore, high-level clinical studies are required on COVID-19 to administrate the effects of vitamins and natural honey.

COVID-19 and L-arginine Supplementations: Yet to Find the Missed Key.

Current coronavirus disease (COVID-19) is regarded as a primary respiratory and vascular disease leading to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and endothelial dysfunction (ED) in severe cases. The causative virus of COVID-19 is SARS-CoV-2, which binds angiotensin-converting enzyme 2 (ACE2) for its entry. It has been shown that ED is linked to various COVID-19 complications since endothelial cells are regarded as the chief barrier against SARS-CoV- 2 invasion. SARS-CoV-2-indued ED leads to endotheliitis and thrombosis due to endothelial nitric oxide (NO) inhibition with subsequent vasoconstriction and tissue hypoxia. Loss of vasodilator NO and anti-thrombin factor from endothelial SARS-CoV-2 infection contribute to the progression of vascular dysfunction and coagulopathy. Therefore, NO restoration improves pulmonary function and hinders viral replication during respiratory viral infections, including COVID-19. L-arginine is a semiessential amino acid that has antiviral and immunomodulatory effects as well as improves the biosynthesis of NO in endothelial cells. L-arginine may reduce the risk of ALI through inhibition of generation of peroxynitrite and suppression of the release of proinflammatory cytokines from alveolar macrophages. Of interest, restoration of NO by L-arginine may attenuate SARS-CoV-2 infection through different mechanisms, including reduction binding of SARS-CoV-2 to ACE2, inhibition of transmembrane protease serine-type 2 (TMPRSS2), critical for the activation of SARS-CoV-2 spike protein and cellular entry, inhibition proliferation and replication of SARS-CoV-2, and prevention of SARS-CoV-2-induced coagulopathy. In conclusion, through antiviral and immunomodulatory effects, L-arginine and released NO have mutual and interrelated actions against SARS-CoV-2 infection.

Graphene-based Nanomaterials in Fighting the Most Challenging Viruses and Immunogenic Disorders.

Viral diseases have long been among the biggest challenges for healthcare systems around the world. The recent Coronavirus Disease 2019 (COVID-19) pandemic is an example of how complicated the situation can get if we are not prepared to combat a viral outbreak in time, which brings up the need for quick and affordable biosensing platforms and vast knowledge of potential antiviral effects and drug/gene delivery opportunities. The same challenges have also existed for nonviral immunogenic disorders. Nanomedicine is considered a novel candidate for effectively overcoming these worldwide challenges. Among the versatile nanomaterials commonly used in biomedical applications, graphene has recently earned much attention thanks to its special and inspiring physicochemical properties, such as its large surface area, efficient thermal/electrical properties, carbon-based chemical purity with controllable biocompatibility, easy functionalization, capability of single-molecule detection, anticancer characteristics, 3D template feature in tissue engineering, and, in particular, antibacterial/antiviral activities. In this Review, the most important and challenging viruses of our era, such as human immunodeficiency virus, Ebola, SARS-CoV-2, norovirus, and hepatitis virus, and immunogenic disorders, such as asthma, Alzheimer's disease, and Parkinson's disease, in which graphene-based nanomaterials can effectively take part in the prevention, detection, treatment, medication, and health effect issues, have been covered and discussed.

Molecular Mechanisms of Possible Action of Phenolic Compounds in COVID-19 Protection and Prevention.

The worldwide outbreak of COVID-19 was caused by a pathogenic virus called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Therapies against SARS-CoV-2 target the virus or human cells or the immune system. However, therapies based on specific antibodies, such as vaccines and monoclonal antibodies, may become inefficient enough when the virus changes its antigenicity due to mutations. Polyphenols are the major class of bioactive compounds in nature, exerting diverse health effects based on their direct antioxidant activity and their effects in the modulation of intracellular signaling. There are currently numerous clinical trials investigating the effects of polyphenols in prophylaxis and the treatment of COVID-19, from symptomatic, via moderate and severe COVID-19 treatment, to anti-fibrotic treatment in discharged COVID-19 patients. Antiviral activities of polyphenols and their impact on immune system modulation could serve as a solid basis for developing polyphenol-based natural approaches for preventing and treating COVID-19.

Possible therapeutic effects of Nigella sativa and its thymoquinone on COVID-19.

CONTEXT: COVID-19 is a novel coronavirus that causes a severe infection in the respiratory system. Nigella sativa L. (Ranunculaceae) is an annual flowering plant used traditionally as a natural food supplement and multipurpose medicinal agent. OBJECTIVE: The possible beneficial effects of N. sativa, and its constituent, thymoquinone (TQ) on COVID-19 were reviewed. METHODS: The key words including, COVID-19, N. sativa, thymoquinone, antiviral effects, anti-inflammatory and immunomodulatory effects in different databases such as Web of Science (ISI), PubMed, Scopus, and Google Scholar were searched from 1990 up to February 2021. RESULTS: The current literature review showed that N. sativa and TQ reduced the level of pro-inflammatory mediators including, IL-2, IL-4, IL-6, and IL-12, while enhancing IFN-γ. Nigella sativa and TQ increased the serum levels of IgG1 and IgG2a, and improved pulmonary function tests in restrictive respiratory disorders. DISCUSSION AND CONCLUSIONS: These preliminary data of molecular docking, animal, and clinical studies propose N. sativa and TQ might have beneficial effects on the treatment or control of COVID-19 due to antiviral, anti-inflammatory and immunomodulatory properties as well as bronchodilatory effects. The efficacy of N. sativa and TQ on infected patients with COVID-19 in randomize clinical trials will be suggested.

Naringenin, a flavanone with antiviral and anti-inflammatory effects: A promising treatment strategy against COVID-19.

At the end of 2019, a novel flu-like coronavirus named COVID-19 (coronavirus disease 2019) was recognized by World Health Organization. No specific treatments exist for COVID-19 at this time. New evidence suggests that therapeutic options focusing on antiviral agents may alleviate COVID-19 symptoms as well as those that lead to the decrease in the inflammatory responses. Flavonoids, as phenolic compounds, have attracted considerable attention due to their various biological properties. In this review, the promising effects and possible mechanisms of action of naringenin, a citrus-derived flavonoid, against COVID-19 were discussed. We searched PubMed/Medline, Science direct, Scopus, and Google Scholar databases up to March 2020 using the definitive keywords. The evidence reviewed here indicates that naringenin might exert therapeutic effects against COVID-19 through the inhibition of COVID-19 main protease, 3-chymotrypsin-like protease (3CLpro), and reduction of angiotensin converting enzyme receptors activity. One of the other mechanisms by which naringenin might exert therapeutic effects against COVID-19 is, at least partly, by attenuating inflammatory responses. The antiviral activity of the flavanone naringenin against some viruses has also been reported. On the whole, the favorable effects of naringenin lead to a conclusion that naringenin may be a promising treatment strategy against COVID-19.