Update on the omicron sub-variants BA.4 and BA.5.

Several nations have recently begun to relax their public health protocols, particularly regarding the use of face masks when engaging in outdoor activities. This is because there has been a general trend towards fewer cases of coronavirus disease 2019 (COVID-19). However, new Omicron sub-variants (designated BA.4 and BA.5) have recently emerged. These two subvariants are thought to be the cause of an increase in COVID-19 cases in South Africa, the United States, and Europe. They have also begun to spread throughout Asia. They evolved from the Omicron lineage with characteristics that make them even more contagious and which allow them to circumvent immunity from a previous infection or vaccination. This article reviews a number of scientific considerations about these new variants, including their apparently reduced clinical severity.

Green Synthesis and Antimicrobial Activities of Silver Nanoparticles Using Calotropis gigantea from Ie Seu-Um Geothermal Area, Aceh Province, Indonesia.

Herein, we report our success synthesizing silver nanoparticles (AgNPs) using aqueous extracts from the leaves and flowers of Calotropis gigantea growing in the geothermal manifestation Ie Seu-Um, Aceh Besar, Indonesia. C. gigantea aqueous extract can be used as a bio-reductant for Ag+→Ag0 conversion, obtained by 48h incubation of Ag+, and the extract mixture in a dark condition. UV-Vis characterization showed that the surface plasmon resonance (SPR) peaks of AgNPs-leaf C. gigantea (AgNPs-LCg) and AgNPs-flower C. gigantea (AgNPs-FCg) appeared in the wavelength range of 410-460 nm. Scanning electron microscopy energy-dispersive X-ray spectrometry (SEM-EDS) revealed the agglomeration and spherical shapes of AgNPs-LCg and AgNPs-FCg with diameters ranging from 87.85 to 256.7 nm. Zeta potentials were observed in the range of -41.8 to -25.1 mV. The Kirby-Bauer disc diffusion assay revealed AgNPs-FCg as the most potent antimicrobial agent with inhibition zones of 12.05 ± 0.58, 11.29 ± 0.45, and 9.02 ± 0.10 mm for Escherichia coli, Staphylococcus aureus, and Candida albicans, respectively. In conclusion, aqueous extract from the leaves or flowers of Calotropis gigantea may be used in the green synthesis of AgNPs with broad-spectrum antimicrobial activities.

An Insight Based on Computational Analysis of the Interaction between the Receptor-Binding Domain of the Omicron Variants and Human Angiotensin-Converting Enzyme 2.

Concerns have been raised about the high number of mutations in the spike protein of the new emergence of the highly transmissible Omicron variant (B.1.1529 lineage) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This variant's extraordinary ability to evade antibodies would significantly impair the current vaccination program. This present study aimed to computationally analyze the interaction between the receptor-binding domain (RBD) in the spike protein of Omicron variants and human angiotensin-converting enzyme 2 (hACE2). The docking results indicated that Omicron BA.2 has exceptionally strong interactions with hACE2 in comparison to Omicron BA.1, Delta, and wild-type, as indicated by various parameters such as salt bridge, hydrogen bond, and non-bonded interactions. The results of the molecular dynamics simulation study corroborate these findings, indicating that Omicron BA.2 has a strong and stable interaction with hACE2. This study provides insight into the development of an effective intervention against this variant.

An Insight Based on Computational Analysis of the Interaction between the Receptor-Binding Domain of the Omicron Variants and Human Angiotensin-Converting Enzyme 2

Concerns have been raised about the high number of mutations in the spike protein of the new emergence of the highly transmissible Omicron variant (B.1.1529 lineage) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This variant's extraordinary ability to evade antibodies would significantly impair the current vaccination program. This present study aimed to computationally analyze the interaction between the receptor-binding domain (RBD) in the spike protein of Omicron variants and human angiotensin-converting enzyme 2 (hACE2). The docking results indicated that Omicron BA.2 has exceptionally strong interactions with hACE2 in comparison to Omicron BA.1, Delta, and wild-type, as indicated by various parameters such as salt bridge, hydrogen bond, and non-bonded interactions. The results of the molecular dynamics simulation study corroborate these findings, indicating that Omicron BA.2 has a strong and stable interaction with hACE2. This study provides insight into the development of an effective intervention against this variant.

Can the SARS-CoV-2 Omicron Variant Confer Natural Immunity against COVID-19?

The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, with no signs of abatement in sight. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of this pandemic and has claimed over 5 million lives, is still mutating, resulting in numerous variants. One of the newest variants is Omicron, which shows an increase in its transmissibility, but also reportedly reduces hospitalization rates and shows milder symptoms, such as in those who have been vaccinated. As a result, many believe that Omicron provides a natural vaccination, which is the first step toward ending the COVID-19 pandemic. Based on published research and scientific evidence, we review and discuss how the end of this pandemic is predicted to occur as a result of Omicron variants being surpassed in the community. In light of the findings of our research, we believe that it is most likely true that the Omicron variant is a natural way of vaccinating the masses and slowing the spread of this deadly pandemic. While the mutation that causes the Omicron variant is encouraging, subsequent mutations do not guarantee that the disease it causes will be less severe. As the virus continues to evolve, humans must constantly adapt by increasing their immunity through vaccination.

Identification of bioactive molecules from Triphala (Ayurvedic herbal formulation) as potential inhibitors of SARS-CoV-2 main protease (Mpro) through computational investigations.

Severe acute respiratory syndrome coronavirus disease (SARS-CoV-2) induced coronavirus disease 2019 (COVID-19) pandemic is the present worldwide health emergency. The global scientific community faces a significant challenge in developing targeted therapies to combat the SARS-CoV-2 infection. Computational approaches have been critical for identifying potential SARS-CoV-2 inhibitors in the face of limited resources and in this time of crisis. Main protease (Mpro) is an intriguing drug target because it processes the polyproteins required for SARS-CoV-2 replication. The application of Ayurvedic knowledge from traditional Indian systems of medicine may be a promising strategy to develop potential inhibitor for different target proteins of SARS-CoV-2. With this endeavor, we docked bioactive molecules from Triphala, an Ayurvedic formulation, against Mpro followed by molecular dynamics (MD) simulation (100 ns) to investigate their inhibitory potential against SARS-CoV-2. The top four best docked molecules (terflavin A, chebulagic acid, chebulinic acid, and corilagin) were selected for MD simulation study and the results obtained were compared to native ligand X77. From docking and MD simulation studies, the selected molecules showed promising binding affinity with the formation of stable complexes at the active binding pocket of Mpro and exhibited negative binding energy during MM-PBSA calculations, indication their strong binding affinity with the target protein. The identified bioactive molecules were further analyzed for drug-likeness by Lipinski's filter, ADMET and toxicity studies. Computational (in silico) investigations identified terflavin A, chebulagic acid, chebulinic acid, and corilagin from Triphala formulation as promising inhibitors of SARS-CoV-2 Mpro, suggesting experimental (in vitro/in vivo) studies to further explore their inhibitory mechanisms.

Computational prediction of the effect of mutations in the receptor-binding domain on the interaction between SARS-CoV-2 and human ACE2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 continues to mutate. Numerous studies have indicated that this viral mutation, particularly in the receptor-binding domain area, may increase the viral affinity for human angiotensin-converting enzyme 2 (hACE2), the receptor for viral entry into host cells, thereby increasing viral virulence and transmission. In this study, we investigated the binding affinity of SARS-CoV-2 variants (Delta plus, Iota, Kappa, Mu, Lambda, and C.1.2) on hACE2 using computational modeling with a protein-protein docking approach. The simulation results indicated that there were differences in the interactions between the RBD and hACE2, including hydrogen bonding, salt bridge interactions, non-bonded interactions, and binding free energy differences among these variants. Molecular dynamics simulations revealed that mutations in the RBD increase the stability of the hACE2-spike protein complex relative to the wild type, following the global stability trend and increasing the binding affinity. The value of binding-free energy calculated using molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) indicated that all mutations in the spike protein increased the contagiousness of SARS-CoV-2 variants. The findings of this study provide a foundation for developing effective interventions against these variants. Computational modeling elucidates that the spike protein of SARS-CoV-2 variants binds considerably stronger than the wild-type to hACE2.

Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach.

Before entering the cell, the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. Hence, this RBD is a critical target for the development of antiviral agents. Recent studies have discovered that SARS-CoV-2 variants with mutations in the RBD have spread globally. The purpose of this in silico study was to determine the potential of a fruit bromelain-derived peptide. DYGAVNEVK. to inhibit the entry of various SARS-CoV-2 variants into human cells by targeting the hACE binding site within the RBD. Molecular docking analysis revealed that DYGAVNEVK interacts with several critical RBD binding residues responsible for the adhesion of the RBD to hACE2. Moreover, 100 ns MD simulations revealed stable interactions between DYGAVNEVK and RBD variants derived from the trajectory of root-mean-square deviation (RMSD), radius of gyration (Rg), and root-mean-square fluctuation (RMSF) analysis, as well as free binding energy calculations. Overall, our computational results indicate that DYGAVNEVK warrants further investigation as a candidate for preventing SARS-CoV-2 due to its interaction with the RBD of SARS-CoV-2 variants.

A Comprehensive Review of the Potential Use of Green Tea Polyphenols in the Management of COVID-19.

Green tea is produced from Camellia sinensis (L.) buds and leaves that have not gone through the oxidation and withering processes used to produce black and oolong teas. It was originated in China, but its cultivation and production have expanded to other Eastern Asian countries. Several polyphenolic compounds, including flavandiols, flavonols, flavonoids, and phenolic acids, are found in green tea and may constitute greater than 30% of the dry weight. Flavonols, especially catechins, represent the majority of green tea polyphenols. Green tea polyphenolic compounds have been reported to confer several health benefits. This review describes the potential use of green tea polyphenols in the management of coronavirus disease 2019 (COVID-19). The immunomodulatory, antibacterial, antioxidant, and anti-inflammatory effects of green tea polyphenols have also been considered in this review. In addition to describing the bioactivities associated with green tea polyphenols, this review discusses the potential delivery of these biomolecules using a nanoparticle drug delivery system. Moreover, the bioavailability and toxicity of green tea polyphenols are also evaluated.

Synthesis of Chitosan-Silver Nanoparticle Composite Spheres and Their Antimicrobial Activities.

Synthesis of silver nanoparticles-chitosan composite particles sphere (AgNPs-chi-spheres) has been completed and its characterization was fulfilled by UV-vis spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and zetasizer nano. UV-vis spectroscopy characterization showed that AgNPs-chi-spheres gave optimum absorption at a wavelength of 410 nm. The XRD spectra showed that the structure of AgNPs-chi-spheres were crystalline and spherical. Characterization by SEM showed that AgNPs-chi-spheres, with the addition of 20% of NaOH, resulted in the lowest average particle sizes of 46.91 nm. EDX analysis also showed that AgNPs-chi-spheres, with the addition of a 20% NaOH concentration, produced particles with regular spheres, a smooth and relatively nonporous structure. The analysis using zetasizer nano showed that the zeta potential value and the polydispersity index value of the AgNPs-chi-sphere tended to increase with an increased NaOH concentration. The results of the microbial activity screening showed that the AgNP-chi-Spheres with highest concentration of NaOH, produced the highest inhibition zone diameters against S. aureus, E. coli, and C. albicans, with inhibition zone diameters of 19.5, 18.56, and 12.25 nm, respectively.

In Silico Evaluation of Iranian Medicinal Plant Phytoconstituents as Inhibitors against Main Protease and the Receptor-Binding Domain of SARS-CoV-2.

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in Wuhan, China, in December 2019. Elderly individuals and those with comorbid conditions may be more vulnerable to this disease. Consequently, several research laboratories continue to focus on developing drugs to treat this infection because this disease has developed into a global pandemic with an extremely limited number of specific treatments available. Natural herbal remedies have long been used to treat illnesses in a variety of cultures. Modern medicine has achieved success due to the effectiveness of traditional medicines, which are derived from medicinal plants. The objective of this study was to determine whether components of natural origin from Iranian medicinal plants have an antiviral effect that can prevent humans from this coronavirus infection using the most reliable molecular docking method; in our case, we focused on the main protease (Mpro) and a receptor-binding domain (RBD). The results of molecular docking showed that among 169 molecules of natural origin from common Iranian medicinal plants, 20 molecules (chelidimerine, rutin, fumariline, catechin gallate, adlumidine, astragalin, somniferine, etc.) can be proposed as inhibitors against this coronavirus based on the binding free energy and type of interactions between these molecules and the studied proteins. Moreover, a molecular dynamics simulation study revealed that the chelidimerine-Mpro and somniferine-RBD complexes were stable for up to 50 ns below 0.5 nm. Our results provide valuable insights into this mechanism, which sheds light on future structure-based designs of high-potency inhibitors for SARS-CoV-2.

Interactions of the Receptor Binding Domain of SARS-CoV-2 Variants with hACE2: Insights from Molecular Docking Analysis and Molecular Dynamic Simulation.

Since the beginning of the coronavirus 19 (COVID-19) pandemic in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been evolving through the acquisition of genomic mutations, leading to the emergence of multiple variants of concern (VOCs) and variants of interest (VOIs). Currently, four VOCs (Alpha, Beta, Delta, and Gamma) and seven VOIs (Epsilon, Zeta, Eta, Theta, Iota, Kappa, and Lambda) of SARS-CoV-2 have been identified in worldwide circulation. Here, we investigated the interactions of the receptor-binding domain (RBD) of five SARS-CoV-2 variants with the human angiotensin-converting enzyme 2 (hACE2) receptor in host cells, to determine the extent of molecular divergence and the impact of mutation, using protein-protein docking and dynamics simulation approaches. Along with the wild-type (WT) SARS-CoV-2, this study included the Brazilian (BR/lineage P.1/Gamma), Indian (IN/lineage B.1.617/Delta), South African (SA/lineage B.1.351/Beta), United Kingdom (UK/lineage B.1.1.7/Alpha), and United States (US/lineage B.1.429/Epsilon) variants. The protein-protein docking and dynamics simulation studies revealed that these point mutations considerably affected the structural behavior of the spike (S) protein compared to the WT, which also affected the binding of RBD with hACE2 at the respective sites. Additional experimental studies are required to determine whether these effects have an influence on drug-S protein binding and its potential therapeutic effect.

An Analysis Based on Molecular Docking and Molecular Dynamics Simulation Study of Bromelain as Anti-SARS-CoV-2 Variants.

The rapid spread of a novel coronavirus known as SARS-CoV-2 has compelled the entire world to seek ways to weaken this virus, prevent its spread and also eliminate it. However, no drug has been approved to treat COVID-19. Furthermore, the receptor-binding domain (RBD) on this viral spike protein, as well as several other important parts of this virus, have recently undergone mutations, resulting in new virus variants. While no treatment is currently available, a naturally derived molecule with known antiviral properties could be used as a potential treatment. Bromelain is an enzyme found in the fruit and stem of pineapples. This substance has been shown to have a broad antiviral activity. In this article, we analyse the ability of bromelain to counteract various variants of the SARS-CoV-2 by targeting bromelain binding on the side of this viral interaction with human angiotensin-converting enzyme 2 (hACE2) using molecular docking and molecular dynamics simulation approaches. We have succeeded in making three-dimensional configurations of various RBD variants using protein modelling. Bromelain exhibited good binding affinity toward various variants of RBDs and binds right at the binding site between RBDs and hACE2. This result is also presented in the modelling between Bromelain, RBD, and hACE2. The molecular dynamics (MD) simulations study revealed significant stability of the bromelain and RBD proteins separately up to 100 ns with an RMSD value of 2 Å. Furthermore, despite increases in RMSD and changes in Rog values of complexes, which are likely due to some destabilized interactions between bromelain and RBD proteins, two proteins in each complex remained bonded, and the site where the two proteins bind remained unchanged. This finding indicated that bromelain could have an inhibitory effect on different SARS-CoV-2 variants, paving the way for a new SARS-CoV-2 inhibitor drug. However, more in vitro and in vivo research on this potential mechanism of action is required.

Molecular docking and dynamics study to explore phytochemical ligand molecules against the main protease of SARS-CoV-2 from extensive phytochemical datasets.

BACKGROUND: The high transmission and pathogenicity of SARS-CoV-2 has led to a pandemic that has halted the world's economy and health. The newly evolved strains and scarcity of vaccines has worsened the situation. The main protease (Mpro) of SARS-CoV-2 can act as a potential target due to its role in viral replication and conservation level. METHODS: In this study, we have enlisted more than 1100 phytochemicals from Asian plants based on deep literature mining. The compounds library was screened against the Mpro of SARS-CoV-2. RESULTS: The selected three ligands, Flemichin, Delta-Oleanolic acid, and Emodin 1-O-beta-D-glucoside had a binding energy of -8.9, -8.9, -8.7 KJ/mol respectively. The compounds bind to the active groove of the main protease at; Cys145, Glu166, His41, Met49, Pro168, Met165, Gln189. The multiple descriptors from the simulation study; root mean square deviation, root mean square fluctuation, radius of gyration, hydrogen bond, solvent accessible surface area confirms the stable nature of the protein-ligand complexes. Furthermore, post-md analysis confirms the rigidness in the docked poses over the simulation trajectories. CONCLUSIONS: Our combinatorial drug design approaches may help researchers to identify suitable drug candidates against SARS-CoV-2.

Data on the docking of phytoconstituents of betel plant and matcha green tea on SARS-CoV-2.

Betel (Piper betle L.) and green tea (Camellia sinensis (L) O. Kuntze) have been used for a long time as traditional medicine. The docking of phytoconstituents contained in the betel plant was evaluated against Mpro, and matcha green tea was evaluated against five target receptors of SARS-CoV-2 as follows: spike ectodomain structure (open state), receptor-binding domain (RDB), main protease (Mpro), RNA-dependent RNA polymerase (RdRp), dan papain-like protease (PLpro). The evaluation was carried out based on the value of binding-free energy and the types of interactions of the amino acids at the receptors that interact with the ligands.

Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study.

Since the outbreak of the COVID-19 (coronavirus disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants using a molecular docking approach to inhibit the main protease (Mpro) and spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina (AV) as a docking engine. A rule of five (Ro5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was performed by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding/ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine, and hydroxychloroquine sulfate (antimalarial drugs recommended by the FDA as emergency drugs) were used. The results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir but were better than chloroquine and hydroxychloroquine sulfate as Mpro inhibitors. This finding implied that several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate, which so far are recommended in the treatment of COVID-19. From quantum chemical DFT calculations, the ascending order of chemical reactivity of selected compounds was pectolinarin > hesperidin > rhoifolin > morin > epigallocatechin gallate. All isolated compounds' C=O regions are preferable for an electrophilic attack, and O-H regions are suitable for a nucleophilic attack. Furthermore, Homo-Lumo and global descriptor values indicated a satisfactory remarkable profile for the selected compounds. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development of drugs to treat infections caused by SARS-CoV-2. The present study identified plant-based compounds that can be further investigated in vitro and in vivo as lead compounds against SARS-CoV-2.

Biochemical and Computational Approach of Selected Phytocompounds from Tinospora crispa in the Management of COVID-19.

A pandemic caused by the novel coronavirus (SARS-CoV-2 or COVID-19) began in December 2019 in Wuhan, China, and the number of newly reported cases continues to increase. More than 19.7 million cases have been reported globally and about 728,000 have died as of this writing (10 August 2020). Recently, it has been confirmed that the SARS-CoV-2 main protease (Mpro) enzyme is responsible not only for viral reproduction but also impedes host immune responses. The Mpro provides a highly favorable pharmacological target for the discovery and design of inhibitors. Currently, no specific therapies are available, and investigations into the treatment of COVID-19 are lacking. Therefore, herein, we analyzed the bioactive phytocompounds isolated by gas chromatography-mass spectroscopy (GC-MS) from Tinospora crispa as potential COVID-19 Mpro inhibitors, using molecular docking study. Our analyses unveiled that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules, with three of them exerting biological activity and warranting further optimization and drug development to combat COVID-19.