Naturally Occurring Xanthones; Biological Activities, Chemical Profiles and In Silico Drug Discovery

Xanthones are widely distributed polyphenols, present commonly in higher plants; Garcinia, Calophyllum, Hypericum, Platonia, Mangifera, Gentiana and Swertia. Xanthone tricyclic scaffold is able to interact with different biological targets, showing antibacterial and cytotoxic effects, as well as potent effects against osteoarthritis, malaria, and cardiovascular diseases. Thus, in this article we focused on pharmacological effects, applications and preclinical studies with the recent updates of xanthon´s isolated compounds from 2017-2020. We found that only α-mangostin, gambogic acid, and mangiferin, have been subjected to preclinical studies with particular emphasis on the development of anticancer, diabetes, antimicrobial and hepatoprotective therapeutics. Molecular docking calculations were performed to predict the binding affinities of xanthone-derived compounds against SARS-CoV-2 Mpro. According to the results, cratoxanthone E and morellic acid demonstrated promising binding affinities towards SARS-CoV-2 Mpro with docking scores of −11.2 and −11.0 kcal/mol, respectively. Binding features manifested the capability of cratoxanthone E and morellic acid to exhibit nine and five hydrogen bonds, respectively, with the key amino acids of the Mpro active site. In conclusion, cratoxanthone E and morellic acid are promising anti-COVID-19 drug candidates that warrant further detailed in vivo experimental estimation and clinical assessment.

Anti-COVID-19 and antidiabetic activities of new oleanane and ursane-type triterpenoids from Salvia grossheimii: an in-silico approach.

Salvia grossheimii is a perennial herb with antidiabetic and cytotoxic constituents. In continuation of our study on S. grosshiemii to identify the bioactive phytochemicals, we have reported the characterization of seven undescribed triterpenoids. The aerial parts of the plant were extracted in dichloromethane and its constituents were isolated using chromatography techniques. The structures of compounds were identified using 1D, 2D NMR, and ESI-MS spectral data. Seven new oleanane- and ursane-type triterpenoids (1-7) were identified in S. grossheimii. The structures of 1-7 were characterized as; 2α-hydroxy-3ß-acetoxy-olean-9(11),12-diene (1), 2α-acetoxy-3ß-hydroxy-olean-9(11),12-diene (2), 3ß-acetoxy-olean-18-ene,2α,11α-diol (3), 2α-hydroxy-3ß-acetoxy-urs-9(11),12-diene (4), 2α-acetoxy-3ß-hydroxy-urs-9(11),12-diene (5), 2α,3ß-diacetoxy-urs-12-ene-11α,20ß-diol (6), 2α,3ß-diacetoxy-urs-9(11),12-diene-20ß-ol (7). Triterpenoids (2, 5, and 7) were intramolecular transesterification or dehydration products of their corresponding isomers or allylic alcohol in the C rings, respectively, produced in-situ during NMR spectroscopy. Virtual screening of 1-7 was performed with molecular docking analysis to identify the potential SARS-CoV-2 and α-glucosidase inhibitors using the smina molecular docking algorithm. The best binding energy values (kcal/mol) against COVID-19 main protease Mpro were calculated for 6 (-8.77) and 7 (-8.68), and the higher binding affinities toward human α-glucosidase were obtained for 2 (-9.39) and 6 (-8.63). This study suggests S. grossheimii as a rich source of bioactive triterpenoids and introduces new natural compounds. Considering the high binding energy values of 2, 6, and 7, these structures could be candidates for anti-COVID-19 and antidiabetic drug development in the future.

Diversity of Coronaviruses with Particular Attention to the Interspecies Transmission of SARS-CoV-2.

In December 2019, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China with serious impacts on global health and economy that is still ongoing. Although interspecies transmission of coronaviruses is common and well documented, each coronavirus has a narrowly restricted host range. Coronaviruses utilize different receptors to mediate membrane fusion and replication in the cell cytoplasm. The interplay between the receptor-binding domain (RBD) of coronaviruses and their coevolution are determinants for host susceptibility. The recently emerged SARS-CoV-2 caused the coronavirus disease 2019 (COVID-19) pandemic and has also been reported in domestic and wild animals, raising the question about the responsibility of animals in virus evolution. Additionally, the COVID-19 pandemic might also substantially have an impact on animal production for a long time. In the present review, we discussed the diversity of coronaviruses in animals and thus the diversity of their receptors. Moreover, the determinants of the susceptibility of SARS-CoV-2 in several animals, with special reference to the current evidence of SARS-CoV-2 in animals, were highlighted. Finally, we shed light on the urgent demand for the implementation of the One Health concept as a collaborative global approach to mitigate the threat for both humans and animals.

SARS-CoV-2 Post Vaccinated Adverse Effects and Efficacy in the Egyptian Population.

Vaccines are the solution to overcome SARS-CoV-2. This study aimed to determine the post-Sinopharm vaccine safety-profile and immunity through antibody titers. Data were collected using a structured questionnaire from Egyptian participants who received two doses of Sinopharm vaccine. Data were divided into three parts, the first and second parts were to detect participants' post-first and second dose symptoms and practices, and the third for the results of IgG anti spike protein antibodies test and laboratory tests. Pain, redness, swelling at the injection site, headache, fatigue, and lethargy were the most common post-vaccine symptoms for both first and second doses. Most of the participants felt mild or no symptoms after vaccination. The symptoms started mostly during the first day post-vaccination and lasted for no more than two days. Forty-nine percent of the participants resulted in positive antibodies tests on day 18 post-vaccination. The average antibody level for vaccinated participants with past SARS-CoV-2 infection was much higher than that for non-past infected participants. These vaccines' administration methods need to be reevaluated by changing the dose, dose interval, adding a third dose, or mixing it with other vaccines with different techniques to improve their protection rates. Further studies are required to validate this finding.

Marine Sulfated Polysaccharides as Promising Antiviral Agents: A Comprehensive Report and Modeling Study Focusing on SARS CoV-2.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is a novel coronavirus strain that emerged at the end of 2019, causing millions of deaths so far. Despite enormous efforts being made through various drug discovery campaigns, there is still a desperate need for treatments with high efficacy and selectivity. Recently, marine sulfated polysaccharides (MSPs) have earned significant attention and are widely examined against many viral infections. This article attempted to produce a comprehensive report about MSPs from different marine sources alongside their antiviral effects against various viral species covering the last 25 years of research articles. Additionally, these reported MSPs were subjected to molecular docking and dynamic simulation experiments to ascertain potential interactions with both the receptor-binding domain (RBD) of SARS CoV-2's spike protein (S-protein) and human angiotensin-converting enzyme-2 (ACE2). The possible binding sites on both S-protein's RBD and ACE2 were determined based on how they bind to heparin, which has been reported to exhibit significant antiviral activity against SARS CoV-2 through binding to RBD, preventing the virus from affecting ACE2. Moreover, our modeling results illustrate that heparin can also bind to and block ACE2, acting as a competitor and protective agent against SARS CoV-2 infection. Nine of the investigated MSPs candidates exhibited promising results, taking into consideration the newly emerged SARS CoV-2 variants, of which five were not previously reported to exert antiviral activity against SARS CoV-2, including sulfated galactofucan (1), sulfated polymannuroguluronate (SPMG) (2), sulfated mannan (3), sulfated heterorhamnan (8), and chondroitin sulfate E (CS-E) (9). These results shed light on the importance of sulfated polysaccharides as potential SARS-CoV-2 inhibitors.

Blue Biotechnology: Computational Screening of Sarcophyton Cembranoid Diterpenes for SARS-CoV-2 Main Protease Inhibition.

The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as Mpro inhibitors with ΔGbinding < -33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against Mpro than darunavir with ΔGbinding values of -43.8 and -34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2.

Beyond the Pandemic: COVID-19 Pandemic Changed the Face of Life.

The COVID-19 pandemic is a serious challenge for societies around the globe as entire populations have fallen victim to the infectious spread and have taken up social distancing. In many countries, people have had to self-isolate and to be confined to their homes for several weeks to months to prevent the spread of the virus. Social distancing measures have had both negative and positive impacts on various aspects of economies, lifestyles, education, transportation, food supply, health, social life, and mental wellbeing. On other hands, due to reduced population movements and the decline in human activities, gas emissions decreased and the ozone layer improved; this had a positive impact on Earth's weather and environment. Overall, the COVID-19 pandemic has negative effects on human activities and positive impacts on nature. This study discusses the impact of the COVID-19 pandemic on different life aspects including the economy, social life, health, education, and the environment.

In silico drug discovery of major metabolites from spices as SARS-CoV-2 main protease inhibitors.

Coronavirus Disease 2019 (COVID-19) is an infectious illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), originally identified in Wuhan, China (December 2019) and has since expanded into a pandemic. Here, we investigate metabolites present in several common spices as possible inhibitors of COVID-19. Specifically, 32 compounds isolated from 14 cooking seasonings were examined as inhibitors for SARS-CoV-2 main protease (Mpro), which is required for viral multiplication. Using a drug discovery approach to identify possible antiviral leads, in silico molecular docking studies were performed. Docking calculations revealed a high potency of salvianolic acid A and curcumin as Mpro inhibitors with binding energies of -9.7 and -9.2 kcal/mol, respectively. Binding mode analysis demonstrated the ability of salvianolic acid A and curcumin to form nine and six hydrogen bonds, respectively with amino acids proximal to Mpro's active site. Stabilities and binding affinities of the two identified natural spices were calculated over 40 ns molecular dynamics simulations and compared to an antiviral protease inhibitor (lopinavir). Molecular mechanics-generalized Born surface area energy calculations revealed greater salvianolic acid A affinity for the enzyme over curcumin and lopinavir with energies of -44.8, -34.2 and -34.8 kcal/mol, respectively. Using a STRING database, protein-protein interactions were identified for salvianolic acid A included the biochemical signaling genes ACE, MAPK14 and ESR1; and for curcumin, EGFR and TNF. This study establishes salvianolic acid A as an in silico natural product inhibitor against the SARS-CoV-2 main protease and provides a promising inhibitor lead for in vitro enzyme testing.

Screening for natural and derived bio-active compounds in preclinical and clinical studies: One of the frontlines of fighting the coronaviruses pandemic.

BACKGROUND: Starting December 2019, mankind faced an unprecedented enemy, the COVID-19 virus. The world convened in international efforts, experiences and technologies in order to fight the emerging pandemic. Isolation, hygiene measure, diagnosis, and treatment are the most efficient ways of prevention and intervention nowadays. The health organizations and global care systems screened the available resources and offered recommendations of approved and proposed medications. However, the search for a specific selective therapy or vaccine against COVID-19 remains a challenge. METHODS: A literature search was performed for the screening of natural and derived bio-active compounds which showed potent antiviral activity against coronaviruses using published articles, patents, clinical trials website (https://clinicaltrials.gov/) and web databases (PubMed, SCI Finder, Science Direct, and Google Scholar). RESULTS: Through the screening for natural products with antiviral activities against different types of the human coronavirus, extracts of Lycoris radiata (L'Hér.), Gentiana scabra Bunge, Dioscorea batatas Decne., Cassia tora L., Taxillus chinensis (DC.), Cibotium barometz L. and Echinacea purpurea L. showed a promising effect against SARS-CoV. Out of the listed compound Lycorine, emetine dihydrochloride hydrate, pristimerin, harmine, conessine, berbamine, 4`-hydroxychalcone, papaverine, mycophenolic acid, mycophenolate mofetil, monensin sodium, cycloheximide, oligomycin and valinomycin show potent activity against human coronaviruses. Additionally, it is worth noting that some compounds have already moved into clinical trials for their activity against COVID-19 including fingolimod, methylprednisolone, chloroquine, tetrandrine and tocilizumab. CONCLUSION: Natural compounds and their derivatives could be used for developing potent therapeutics with significant activity against SARS-COV-2, providing a promising frontline in the fighting against COVID-19.

Comprehensive Overview on Multiple Strategies Fighting COVID-19.

Lately, myriad of novel viruses have emerged causing epidemics such as SARS, MERS, and SARS-CoV-2, leading to high mortality rates worldwide. Thus, these viruses represented a challenging threat to mankind, especially considering the miniscule data available at our disposal regarding these novel viruses. The entire world established coordinative relations in research projects regarding drug and vaccine development on the external range, whereas on the internal range, all countries declared it an emergency case through imposing different restrictions related to their border control, large gatherings, school attendance, and most social activities. Pandemic combating plans prioritized all sectors including normal people, medical staff politicians, and scientists collectively shouldered the burden. Through planning and learning the previous lessons from SARS and MERS, healthcare systems could succeed in combating the viral spread and implications of these new pandemics. Different management strategies including social distance, social awareness and isolation represented successful ways to slow down the spread of the pandemic. Furthermore, pre-preparedness of some countries for emergencies is crucial to minimize the consequences of the crisis.