Approaches for prevention and environmental management of novel COVID-19.

The World Health Organization (WHO) recognized a novel coronavirus as the causative agent of a new form of pneumonia. It was subsequently named COVID-19 and reported as the source of a respiratory disease occurrence starting in December 2019 in Wuhan, Hubei Province, China. It has been affirmed a public health emergency of international significance by the World Health Organization. It is regarded as a subset of the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS); COVID-19 is triggered by a betacoronavirus called SARS-CoV-2, which affects the lower respiratory tract and occurs in humans as pneumonia. A variety of drugs, such as remdesivir and favipiravir, are currently undergoing clinical trials to evaluate for the management of COVID-19. The effect of the pandemic as well as the epidemic that follows through the life cycles of various recycled plastic is evaluated, particularly those required for personal safety and health care. In response to the growth in COVID-19 cases worldwide, the energy and environmental impacts of these lifecycle management have risen rapidly. However, significant hazardous waste management concerns arise due to the need to assure the elimination of residual pathogens in household and medical wastes. This review article summarizes the preventive and environmental management of COVID-19.

Screening, molecular simulation & in silico kinetics of virtually designed covid-19 main protease inhibitors.

Coronavirus (covid-19) infection is considered to be deadliest ever pandemic experienced by the human being. It has very badly affected the socio-economic health of human and stuck the scientific community to think and rethink about its complete eradication. But due to no effective treatment or unavailability of vaccine the health professional could not show any significant improvement to control the pandemic. The situation needs newer molecule, vaccine or effective treatment to control covid-19 infection. Different target in viruses has been explored and proteases enzymes were found to be therapeutically effective target for the design of potential anti-covid-19 molecule as it plays the vital role in viral replication and assembly. Structure-based drug design was employed to discover the small molecule of anti-covid-19. Here we considered the small library of naturally occurring polyphenolic compounds and molecular docking, Molecular dynamics (MD) simulations, free binding energy calculation and in-silico ADME calculations to identify the newer HITs. Based upon their score the two molecules were identified as promising candidate. The docking scores were found to be -7.643 and -7.065 for the HIT1 and HIT-2 respectively. In MD simulations study the RMSD values were found to be 4.3 Å & 4.9 Å respectively. To validate these results MM-GBSA was performed and their binding free energies were computationally determined. The prime energy values of identified HITs (-13412.45 & -13441.8 kJ/mole) were found to be very close proximity to reference molecule (-13493.05 kJ/mole). Then in-silico ADME calculations were performed to calculate the drug likeliness identified HITs. BY considering all the values comparative to reference molecule and obtained in-silico pharmacokinetic properties of identified HITs we can suggest that HIT-1 and HIT-2 would be the most promising molecules that can inhibit the main protease enzyme of covid-19. These two molecules would become the potential drug candidate for the treatment of covid-19 infections.

The relationship between hydroxychloroquine plasma concentration and COVID-19 outcomes in rheumatoid arthritis patients in Saudi Arabia.

Background: The drug hydroxychloroquine (HCQ) is widely used to treat rheumatoid arthritis (RA) and has been repurposed for the treatment of COVID-19. This study aims to determine whether HCQ concentration levels in individuals with RA alter the incidence of COVID-19 or its complications. Methods: We collected plasma samples from 13 individuals with confirmed rheumatoid arthritis (RA) to measure HCQ concentration levels. The study included individuals at least 18 years old who had been taking HCQ for at least six months at daily doses ranging from 200 to 400 mg. Results: The study enrolled a total of 13 RA patients. All patients were chronic HCQ users. Among the 13 patients, 7 patients were receiving HCQ at a dose of 200 mg per day, and 6 patients were receiving HCQ at a dose of 400 mg per day. COVID-19 confirmed cases accounted for approximately 46% of all patients. Half of the infected patients (n = 3) were taking a daily dose of 200 mg daily, while the other half were taking 400 mg daily. COVID-19 symptoms ranged from mild to moderate, and the intensity of the symptoms was not severe enough to necessitate hospitalization. COVID-19 symptoms in RA patients included headache, fever, fatigue, dry cough, and loss of taste or smell. Conclusions: Our findings indicated that there was no correlation between HCQ concentrations in rheumatoid arthritis patients and the occurrence of COVID-19 or its complications.

An in-silico investigation of potential natural polyphenols for the targeting of COVID main protease inhibitor.

The deadliest recent pandemic outbreak of COVID-19 disease has severely damaged the socio-economic health of the people globally. Due to unavailability of any effective vaccine or treatment the human beings are still struggling to overcome the pandemic condition. In an attempt to discover anti-COVID molecule, we used in-silico approach and reported 160 natural polyphenols to identify the most promising druggable HITs that can further used for drug discovery process. The co-crystallized structure COVID protease enzyme (PDB id 6LU7) was used. HTVS, MD simulation, binding energy calculations and in-silico ADME calculation were done and analyzed. Depending upon the scores three compounds galangin, nalsudaldain and rhamnezine were identified and the docking score were found to be -7.704, -6.51, -4.212 respectively. These docked complexes were further subjected to MD simulation runs over a 100 ns time and the RMSD and RMSF values were determined. The RMSD values of three compounds were found to be 2.9 Å, 7.6 Å & 9.5 Å respectively and the lowest RMSF values suggested the steady stability of ligand-protein complexes. The binding free energies (ΔG) of compounds with protein were found to be -49.8, -56.45, -62.87 kJ/mole. Moreover, in-silico ADME calculations indicated the drug likeliness properties of these molecules. By considering all these in-silico results the identified HITs would be the most probable anti-COVID drug molecules that can be further taken in wet lab and can act as lead for development of newer inhibitor of COVID-19 main protease enzyme.

Computational Study of the Phytochemical Constituents from Uncaria tomentosa Stem Bark against SARS-CoV-2 Omicron Spike Protein

The SARS-CoV-2 Omicron variant has spread rapidly and is considered the predominant variant in the world, and its main characteristic is related to evade immunity from natural infection or vaccines, due to its multiple mutations in the spike protein. On the other hand, medicinal plants have been used as alternatives therapies to ameliorate some signs and symptoms in COVID-19, and in our previous work, the cat's claw (Uncaria tomentosa) stem bark has been studied in vitro and showed antiviral activity on SARS-CoV-2 as well as in silico studies on the 3CLpro protein and as disruptor between the ACE-2 human receptor and the spike protein. The aim in this computational study was to determine the main phytochemical constituents from U. tomentosa stem bark against the SARS-CoV-2 Omicron spike protein based on molecular modeling. A molecular docking was carried out on the isolated phytochemicals in a previous work against the SARS-CoV-2 Omicron spike protein-binding domain (PDB ID: 7T9K). Next, a molecular dynamic study was carried out to monitor the stability during the MD simulations. As results proanthocyanidin-C1 (-10.76 kcal/mol), quinovic acid-type 2 (-9.86 kcal/mol), and proanthocyanidin-B2 (-9.82 kcal/mol) were the constituents with the best binding free energy on the SARS-CoV-2 Omicron spike protein, and the best compound was stable during the dynamic simulation under physiological conditions. It is concluded that the anthocyanidin-based compounds determined in the stem bark ethanol extract could be responsible for the potential antiviral activity on SARS-CoV-2 Omicron variant, and the proanthocyanidin-C1 emerged as a powerful candidate to combat new variants. [ FROM AUTHOR] Copyright of Journal of Chemistry is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Effect of chronic hydroxychloroquine use on COVID-19 risk in patients with rheumatoid arthritis and systemic lupus erythematosus: a multicenter retrospective cohort.

OBJECTIVE: Hydroxychloroquine (HCQ) has been used during the coronavirus disease 2019 (COVID-19) pandemic because of its reported anti-viral activity. This study examined the association of chronic HCQ use with the incidence and complications of COVID-19. METHODS: This retrospective cohort study included adults with rheumatoid arthritis and/or systemic lupus erythematosus who visited rheumatology clinics in three tertiary hospitals in Riyadh, Saudi Arabia between January 2019 and December 2020. Patients were categorized into two groups based on HCQ use. Data were obtained from the electronic health record and by interviews with patients. The primary study objective was the incidence of COVID-19 and its complications from March 2020 to February 2021. RESULTS: Almost 11% of the study cohort was positive for COVID-19, and the incidence of COVID-19 was similar between HCQ users (11.11%) and nonusers (10.86%). Disease complication rates were similar in the study arms, and they mainly included fever, dry cough, fatigue, and breathing difficulty. CONCLUSIONS: This study revealed no significant association between chronic HCQ use and the incidence of COVID-19, and disease complications were similar in the study arms.

Design & discovery of small molecule COVID-19 inhibitor via dual approach based virtual screening and molecular simulation studies.

The emerged COVID-19 (SARS corona virus) pandemic leads to severe or fatal respiratory tract infections affecting millions of people worldwide since its outbreak. The situation needs the newer molecule to control the infections as the pandemic had very badly affected the health and socioeconomic conditions of human being. CoV-2 main protease is considered to be key enzyme by targeting which we can design or develop the drug candidate. The active fitting and binding of any molecule depends upon the shape and electrostatic properties of ligand complementary to the receptor site. In this study ZINC13 database, a drug like subset (13,195,609 molecules) was subjected to shape and electrostic based virtual screening (VROCS & EON software) and followed by molecular modelling studies using docking and molecular dynamics simulation. Further the drug ability of identified candidate was predicted by the SiteMap analysis. The best shape and electrostatic similarities were observed between ZINC19973962 and reference molecule. The Tamintoshape and Tanimotoelectrostatic was found to be 0.667 and 0.022 respectively. The molecule also displayed the identical binding pattern with docking score -7.964 and this interaction was further validated by the molecular dynamics simulations. The RMSD & RMSF values were found to be 1.5 Å and1.8 Å respectively suggesting the stability of complex and very low fluctuation in ligand-protein complex over the entire MD simulation run. SiteMap analysis showed the identical Dscore of reference and identified HIT that indicated the molecule ZINC19973962 would be the promising druggable candidate against COVID main protease enzyme and can be used as lead molecule for the development of anti-COVID molecule.

COVID-19 Outbreak: Pathogenesis, Current Therapies, and Potentials for Future Management.

At the end of 2019, a novel coronavirus (CoV) was found at the seafood market of Hubei province in Wuhan, China, and this virus was officially named coronavirus diseases 2019 (COVID-19) by World Health Organization (WHO). COVID-19 is mainly characterized by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) and creates public health concerns as well as significant threats to the economy around the world. Unfortunately, the pathogenesis of COVID-19 is unclear and there is no effective treatment of this newly life-threatening and devastating virus. Therefore, it is crucial to search for alternative methods that alleviate or inhibit the spread of COVID-19. In this review, we try to find out the etiology, epidemiology, symptoms as well as transmissions of this novel virus. We also summarize therapeutic interventions and suggest antiviral treatments, immune-enhancing candidates, general supplements, and CoV specific treatments that control replication and reproduction of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV).

Available Compounds With Therapeutic Potential Against COVID-19: Antimicrobial Therapies, Supportive Care, and Probable Vaccines.

The recent outbreak of the COVID-2019 (coronavirus disease 2019) due to the infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has realized the requirement of alternative therapeutics to mitigate and alleviate this lethal infection. These alternative therapies are effective when they are started at the initial stage of the infection. Some drugs that were used in previous other related infections SARS-CoV-2003 and Middle East respiratory syndrome coronavirus (MERS-CoV)-2012 could be potentially active against currently emerging SARS-CoV-2. This fact imparts some rationale of current interventions, in the absence of any specific therapeutics for SARS-CoV-2. It is imperative to focus on the available antimicrobial and adjunct therapies during the current emergency state and overcome the challenges associated with the absence of robust controlled studies. There is no established set of drugs to manage SARS-CoV-2 infected patients. However, closely following patients' conditions and responding with the dosage guidelines of available drugs may significantly impact our ability to slow down the infection. Of note, it depends upon the condition of the patients and associated comorbid; therefore, the health workers need to choose the drug combinations judiciously until COVID-19 specific drug or vaccine is developed with the collective scientific rigor. In this article, we reviewed the available antimicrobial drug, supportive therapies, and probable high importance vaccines for the COVID-19 treatment.

Antioxidant, Antibacterial, and Anticancer Activities of Bitter Gourd Fruit Extracts at Three Different Cultivation Stages

In this study, we are presenting the effect of three ripening stages of air-dried bitter gourd fruit extracts on phenolic acid composition, antioxidant, antibacterial, and anticancer activities. The results showed mature bitter gourd fruit extract in 100% methanol showing 78% DPPHº scavenging activity. Immature dried fruit extract in 80% and 100% methanol showed promising antibacterial activities, i.e., 18.5 ± 0.21 mm zone-of-inhibition against Staphylococcus aureus, while mature dried fruit extract in 80% methanol showed 18.4 ± 0.17 mm zone-of-inhibition against Escherichia coli. Anticancer activity results of 100% methanol extracts of ripened fruit possess showed 6.72 ± 1.81 and 3.55 ± 0.51 mg/mL IC50 values with HeLa and MDBK cancer cell lines, respectively. The overall results indicate that the immature and ripen fruits of BG could be extracted in pure methanol as an antibacterial and anticancer phytomedicine.

Effect of essential oils on the immune response to some viral vaccines in broiler chickens, with special reference to Newcastle disease virus.

This trial assessed the efficacy of a commercial essential oil (EO) product on the immune response to vaccination against Newcastle disease (ND) and subsequent challenge with virulent ND virus genotype VII (vNDv genotype VII) by using the following experimental groups of broiler chickens (Each group had 21 birds with 3 replicates in each, n = 7): NC (negative control), PC (positive control), VC (vaccinated), and VTC (vaccinated and treated with EOs). Moreover, in a trial to study the effect of EOs on vNDv genotype VII in vivo as a preventive or therapeutic measure, 2 additional ND-vaccinated groups were used (PRV: medicated 1 D before vNDv challenge for 5 D; and TTT: medicated 2 D after vNDv challenge for 5 D). In addition, the immune-modulatory effect of EOs on the avian influenza (AI), infectious bronchitis (IB), and infectious bursal disease (IBD) vaccines was assessed through the serological response. The use of EOs along with administration of ND vaccines (VTC) revealed a lower mortality rate (42.86%), clinical signs, and postmortem lesion score (11) than ND vaccines alone (VC) (52.28% mortality and score 15), in addition to lower hemagglutination inhibition (P < 0.05) (6.5 ± 0.46) and viral shedding (10 log 2.28 ± 0.24) titres 1 wk after challenge in comparison with VC (8.63 ± 0.65 and 10 log 3.29 ± 0.72, respectively). Nevertheless, the EOs mixture (VTC) (1952 ± 28.82) did not significantly (P > 0.05) improve growth performance compared with the nontreated birds (NC and VC) (1970 ± 19.56 and 1904 ± 38.66). EOs showed an antiviral effect on vNDv in vivo (in chickens) as a preventive measure (PRV) as well as some therapeutic effect (TTT) through decreasing the viral shedding titres (loNC0), mortality rate, and severity of clinical signs and postmortem lesions, in addition to serum malondialdhyde level. Regarding the other viruses, the EOs mixture did not improve the immune response to the AI and IB vaccines but significantly (P < 0.05) increased the ELISA antibody titre for IBD virus at the 28th D of age (2,108 ± 341.05). The studied EOs mixture showed an immune-stimulating response to ND and IBD vaccines, antiviral effect against ND virus, especially if administered before the challenge; however, it did not have a growth-promoting effect.