New Ways to Protect the Host from SARS-CoV-2? Lung Microbiome Metabolites Inhibit STAT3 and Modulate the Immunological Network.

COVID-19 caused by the SARS-CoV-2 infection is a systemic disease that affects multiple organs, biological pathways, and cell types. A systems biology approach would benefit the study of COVID-19 in the pandemic as well as the endemic state. Notably, patients with COVID-19 have dysbiosis of lung microbiota whose functional relevance to the host is largely unknown. We carried out a systems biology investigation of the impact of lung microbiome-derived metabolites on host immune system during COVID-19. RNAseq was performed to identify the host-specific pro- and anti-inflammatory differentially expressed genes (DEGs) in bronchial epithelium and alveolar cells during SARS-CoV-2 infection. The overlapping DEGs were harnessed to construct an immune network while their key transcriptional regulator was deciphered. We identified 68 overlapping genes from both cell types to construct the immune network, and Signal Transducer and Activator of Transcription 3 (STAT3) was found to regulate the majority of the network proteins. Furthermore, thymidine diphosphate produced from the lung microbiome had the highest affinity with STAT3 (-6.349 kcal/mol) than the known STAT3 inhibitors (n = 410), with an affinity ranging from -5.39 to 1.31 kcal/mol. In addition, the molecular dynamic studies showed distinguishable changes in the behavior of the STAT3 complex when compared with free STAT3. Overall, our results provide new observations on the importance of lung microbiome metabolites that regulate the host immune system in patients with COVID-19, and may open up new avenues for preventive medicine and therapeutics innovation.

The SARS-CoV-2 Virus could Downregulate Dual Specificity Phosphatase-1 Expression in Oral Cancer: A Plausible Hypothesis that could Explain Oral Cancer Progression in the COVID-19 Pandemic and Post-pandemic Situation.

This study explores the downregulation of Dual Specificity Phosphatase-1 (DUSP-1) expression in oral cancer progression during the pandemic and post-pandemic situations. Keywords: COVID-19, Dual specificity phosphatase-1, Oral cancer, SARS-CoV-2.

COVID-19: Ramifications and Effects on University Healthcare Students.

AIM: This study was carefully designed to analyze the perceived psychological impact of the COVID-19 pandemic among Roseman dental students. Students assessed their perceived changes in stress, self-esteem, and lifestyle behavior changes based on the impact of the pandemic. MATERIALS AND METHODS: A self-designed, anonymous, 18-item questionnaire was administered to Roseman dental students after being approved by the Institutional Review Board. Independent samples t-test and one-way ANOVA were utilized for comparison of psychological factors toward gender, as well as year of study. Chi-square correlations between stress and self-esteem, as well as lifestyle behavior, were also reported. RESULTS: In total, 313 students with a mean age of 28.15 (SD:4.21) completed the survey. Statistically significant differences were shown between students based upon age and year of study, with regard to stress and lifestyle behavior changes. Cross-tabulations of stress with self-esteem and lifestyle behavior changes showed positive relationships, as students with higher levels of stress showed significant self-esteem problems and lifestyle behavior changes. The largest frequency of stress/anxiety and lifestyle behavioral changes was found in the age range of 25-34 years old, particularly in the Class of 2024 and 2025. CONCLUSION: The COVID-19 pandemic has imposed a significant psychological impact on dental students at Roseman. However, further studies are needed to assess the long-lasting impacts of the pandemic on University healthcare students as a whole. CLINICAL SIGNIFICANCE: The pandemic has not only affected the way in which dental students progress academically but also as healthcare providers now and into the future.

Repurposing of potential antiviral drugs against RNA-dependent RNA polymerase of SARS-CoV-2 by computational approach.

The high incidences of COVID-19 cases are believed to be associated with high transmissibility rates, which emphasizes the need for the discovery of evidence-based antiviral therapies for curing the disease. The rationale of repurposing existing classes of antiviral small molecule therapeutics against SARS-CoV-2 infection has been expected to accelerate the tedious and expensive drug development process. While Remdesivir has been recently approved to be the first treatment option for specific groups of COVID-19 patients, combinatory therapy with potential antiviral drugs may be necessary to enhance the efficacy in different populations. Hence, a comprehensive list of investigational antimicrobial drug compounds such as Favipiravir, Fidaxomicin, Galidesivir, GC376, Ribavirin, Rifabutin, and Umifenovir were computationally evaluated in this study. We performed in silico docking and molecular dynamics simulation on the selected small molecules against RNA-dependent RNA polymerase, which is one of the key target proteins of SARS-CoV-2, using AutoDock and GROMACS. Interestingly, our results revealed that the macrocyclic antibiotic, Fidaxomicin, possesses the highest binding affinity with the lowest energy value of -8.97 kcal/mol binding to the same active sites of RdRp. GC376, Rifabutin, Umifenovir and Remdesivir were identified as the next best compounds. Therefore, the above-mentioned compounds could be considered good leads for further preclinical and clinical experimentations as potentially efficient antiviral inhibitors for combination therapies against SARS-CoV-2.

Multi-target potential of Indian phytochemicals against SARS-CoV-2: A docking, molecular dynamics and MM-GBSA approach extended to Omicron B.1.1.529.

BACKGROUND: SARS-CoV-2, an emerged strain of corona virus family became almost serious health concern worldwide. Despite vaccines availability, reports suggest the occurrence of SARS-CoV-2 infection even in a vaccinated population. With frequent evolution and expected multiple COVID-19 waves, improved preventive, diagnostic, and treatment measures are required. In recent times, phytochemicals have gained attention due to their therapeutic characteristics and are suggested as alternative and complementary treatments for infectious diseases. This present study aimed to identify potential inhibitors against reported protein targets of SARS-CoV-2. METHODOLOGY: We computationally investigated potential SARS-CoV-2 protein targets from the literature and collected druggable phytochemicals from Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT) database. Further, we implemented a systematic workflow of molecular docking, dynamic simulations and generalized born surface area free-energy calculations (MM-GBSA). RESULTS: Extensive literature search and assessment of 1508 articles identifies 13 potential SARS-CoV-2 protein targets. We screened 501 druggable phytochemicals with proven biological activities. Analysis of 6513(501 *13) docked phytochemicals complex, 26 were efficient against SARS-CoV-2. Amongst, 4,8-dihydroxysesamin and arboreal from Gmelina arborea were ranked potential against most of the targets with binding energy ranging between - 10.7 to - 8.2 kcal/mol. Additionally, comparative docking with known drugs such as arbidol (-6.6 to -5.1 kcal/mol), favipiravir (-5.5 to -4.5 kcal/mol), hydroxychloroquine (-6.5 to -5.1 kcal/mol), and remedesivir (-8.0 to -5.3 kcal/mol) revealed equal/less affinity than 4,8-dihydroxysesamin and arboreal. Interestingly, the nucleocapsid target was found commonly inhibited by 4,8-dihydroxysesamin and arboreal. Molecular dynamic simulation and Molecular mechanics generalized born surface area (MM-GBSA)calculations reflect that both the compounds possess high inhibiting potential against SARS-CoV-2 including the recently emerged Omicron variant (B.1.1.529). CONCLUSION: Overall our study imparts the usage of phytochemicals as antiviral agents for SARS-CoV-2 infection. Additional in vitro and in vivo testing of these phytochemicals is required to confirm their potency.

Does Social Media have any Influence during the COVID-19 Pandemic? An Update.

AIM: The study aimed to explore the role, impact, and influence of social media on the population during the coronavirus disease-2019 (COVID-19)pandemic. BACKGROUND: During pandemics, communication is an important factor to disseminate the information, create awareness and provide timely updates from authorized personnel to the masses. Social media progressed to function as a mediator of transmission of information between the government and authorities and the public during the COVID-19. REVIEW RESULTS: Though several strengths were observed yet liabilities did not go unnoticed regarding the role essayed by social media during this pandemic period. When used responsibly, these technologies can aid in the rapid dissemination of crucial facts, important scientific discoveries, and information regarding diagnosis, treatment, and follow-up as well as comparing different strategies across the world. It is recommended to follow certain fundamental standards while exchanging information on social media networks during the COVID-19 era in order to utilize these technologies responsibly and effectively. CONCLUSION: In this research, we have made an attempt to synthesize the vital facts regarding the impact, benefits, and drawbacks of using social media during COVID-19. Eventually, the decision of evaluation, acceptance, and denial of the information received rests with the individual. CLINICAL SIGNIFICANCE: Social media use has become intangible with health care. Instead of venturing out the negative effects, we need to focus on utilizing social media for the betterment of the public and to the advantage of the public to increase awareness levels, spread knowledge, and cooperate to tap the benefits to the maximum extent possible to prevent the disease spread.

Effectiveness of Online Learning vs Traditional Learning during COVID-19 Pandemic in Chennai: A Questionnaire Study.

BACKGROUND: Digitalization of education became a need of the hour when the COVID-19 pandemic affected the traditional modalities of learning, and it was widely implemented in various fields including dentistry. AIMS: The aim of this study was to assess the effectiveness of online learning against traditional learning systems among dental students in Chennai. METHODS AND MATERIALS: A Google Form questionnaire comprising 29 dental learning-based questions was designed and distributed to dental students across colleges in Chennai using online distribution platforms. The study responses were closed after the stipulated period of 1 month. The data were analyzed using SPSS software version 17. RESULTS: The survey was answered by 834 participants comprising 76.9% females and 22.3% males. Of the total study population, 71.1% of them did not have previous online learning experiences. Approximately, 15.5% of the study population were not satisfied with the facilities provided by the online learning platforms. Also, one-third of the study population reported difficulty during the presentation. Three-fourths of the study participants did not prefer online learning over traditional learning and reported that the attention span and communication between the students and teachers were lower in online classes. Overall, 43% of the study participants rated the quality of online video-based learning to be good and 8.5% found it to be poor. CONCLUSION: Online-based learning systems are evolving and can provide a wide array of knowledge from global experts. However, structured planning and technique may be needed for the dental curriculum.

Alternate Special Stains for the Detection of Mycotic Organisms in Oral Cyto-Smears-A Histomorphometric Study.

In the wake of the COVID-19 pandemic, fungal infections of the maxillofacial region have become prevalent, making their accurate diagnosis vital. Histopathological staining remains a simple, cost-effective technique for differentiation and diagnosis of the causative fungal organisms. The present study aims to evaluate the staining efficacy of Periodic Acid-Schiff (PAS), Alcian Blue, Safranin-O and Gomori's Methenamine Silver (GMS) on fungal smears. This research work also attempts to study the morphometric characteristics of Candida albicans, Aspergillus flavus, Rhizopus oryzae. Candida albicans, Aspergillus flavus and Rhizopus oryzae, 10 smears each, were stained using PAS, Alcian Blue, Safranin-O and GMS. The morphological characteristics and staining efficacy were examined, and semi-quantitative scoring was performed. Candida albicans, Aspergillus flavus and Rhizopus oryzae were stained for the first time with Safranin-O. The morphometric traits were then analyzed using an image analysis software. Safranin-O provided the most reliable staining efficacy amongst the stains and optimum morphological definition for all three organisms. Safranin-O was found to be superior to PAS and GMS, ensuring detection of even the most minute mycotic colonies. The hyphae of Aspergillus flavus to be the largest, and the spores and fruiting body of Rhizopus oryzae were found to be the largest amongst the three organisms compared. Early and accurate diagnosis of fungal infections can significantly reduce morbidity in orofacial fungal infections.

Resveratrol and Its Natural Analogues Inhibit RNA Dependant RNA Polymerase (RdRp) of Rhizopus oryzae in Mucormycosis through Computational Investigations

Mucormycosis (or black fungus infection) is a life-threatening, but rare fungal infection with predominant occurrence in immunosuppressed patients following the SARS-CoV-2 infection. Rhizopus oryzae (R. O.) causes about 70% of all cases of mucormycosis. RNA dependent RNA polymerase (RdRp) is a key fungal protein implicated in the genome replication and multiplication of R. oryzae. In view of biological significance of resveratrol (RES), rich in grape skin extract, on various microbial infections and inflammatory diseases including gum infections and periodontitis, our present study was aimed at in silico investigation of RES and its two natural analogues, piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene, PIC), and 3,5,4'-trimethoxy-trans-stilbene (TMS) for their development as successful antifungal agents targeting the R. O. specific RdRp to combat the deadly mucormycosis. Due to the unavailability of the three-dimensional structure of R. O. RdRp in the Protein Database Bank (PDB), the protein structure of RdRp was modeled using the target sequence of RT/Duplex (Set-Met) (PDB ID: 6AR3, 3.41 Å) by homology modeling. Using the modeled structure of R. O. RdRp, docking and molecular dynamics (MD) simulation studies were carried out in Schrödinger suite version 2021-2 software. The findings of docking, MD simulations and MM-PBSA binding energies conclude that the RES, PIC and TMS possess predictable and stable binding affinity/interactions to the R. O. RdRp. These bioactive compounds could potentially inhibit the activity of R. O. RdRp. Further, density function theory (DFT) analysis (B3LYP, 6-311 G* basis set) was performed, and results of DFT analysis indicate that the compound PIC could be a more potential inhibitor for R. O. RdRp over RES. In in silico drug-likeness and ADMET prediction studies, all of the compounds exhibited acceptable drug-likeness, the Lipinski’s rule of five and pharmacokinetic parameters. Finally, it can be concluded that RES and its two natural analogues, PIC and TMS are the potential inhibitors of R. O. RdRp based on docking, MD and DFT studies. [ FROM AUTHOR] Copyright of Polycyclic Aromatic Compounds is the property of Taylor & Francis Ltd 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.)

Severe Acute Respiratory Syndrome Coronavirus 2 Nosode: A Potential Alternative Vaccine Platform.

Besides conventional vaccinations, viable alternatives are needed to elicit an immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We propose and highlight the value of a homeopathic approach known as the "nosode" for the prevention of coronavirus disease-2019 (COVID-19). Nosode is an extract prepared from disease-affected tissues which is subsequently processed and administered as an antidote for the same medical condition. This concept might be a crucial therapeutic approach for viral infections since infected tissues contain a wide range of important viral antigens that could induce a functional host response via immunological sensitization. Thereby, nosode preparation produced from SARS-CoV-2-affected tissues may provide protection against COVID-19. "SARS-CoV-2 nosode" warrants more scientific investigation as a viable alternative vaccination platform. Keywords: COVID-19, Nosode, SARS-CoV-2, Variolation.

Receptor binding domain of SARS-CoV-2 from Wuhan strain to Omicron B.1.1.529 attributes increased affinity to variable structures of human ACE2.

BACKGROUND: COVID-19 is an infectious disease declared as a global pandemic caused by SARS-CoV-2 virus. Genomic changes in the receptor binding domain (RBD) region of SARS-CoV-2 led to an increased, infectivity in humans through interaction with the angiotensin-converting enzyme2 (ACE2) receptor. Simultaneously, the genetic variants in ACE2 provide an opportunity for SARS-CoV-2 infection and severity. We demonstrate the binding efficiencies of RBDs of SARS-CoV-2 strain with ACE2 variants of the human host. METHODOLOGY: A Total of 615 SARS-CoV-2 genomes were retrieved from repository. Eighteen variations were identified contributing to structural changes in RBD that are distributed in 615 isolates. An analyses of 285 single nucleotide variances at the coding region of the ACE2 receptor showed 34 to be pathogenic. Homology models of 34 ACE2 and 18 RBD structures were constructed with 34 and 18 structural variants, respectively. Protein docking of 612 (34 *18) ACE2-RBD complexes showed variable affinities compared to wildtype Wuhan's and other SARS-CoV-2 RBDs, including Omicron B.1.1.529. Finally, molecular dynamic simulation was performed to determine the stability of the complexes. RESULTS: Among 612, the top 3 complexes showing least binding energy were selected. The ACE2 with rs961360700 variant showed the least binding energy (-895.2 Kcal/mol) on binding with the RBD of Phe160Ser variant compared to Wuhan's RBD complex. Interestingly, the binding energy of RBD of Omicron B.1.1.529 with ACE2 (rs961360700) structure showed least binding energy of -1010 Kcal/mol. Additionally, molecular dynamics showed structure stability for all the analysed complexes with the RMSD (0.22-0.26 nm), RMSF (0.11-0.13 nm), and Rg (2.53-2.56 nm). CONCLUSION: In conclusion, our investigation highlights the clinical variants contributing to structural variants in ACE2 receptors that lead to efficient binding of SARS-CoV-2. Therefore, screening of these ACE2 polymorphisms will help detect COVID-19 risk population so as to provide additional care and for safe management.

Plant-Derived Antiviral Compounds as Potential Entry Inhibitors against Spike Protein of SARS-CoV-2 Wild-Type and Delta Variant: An Integrative in SilicoApproach.

The wild-type SARS-CoV-2 has continuously evolved into several variants with increased transmissibility and virulence. The Delta variant which was initially identified in India created a devastating impact throughout the country during the second wave. While the efficacy of the existing vaccines against the latest SARS-CoV-2 variants remains unclear, extensive research is being carried out to develop potential antiviral drugs through approaches like in silico screening and drug-repurposing. This study aimed to conduct the docking-based virtual screening of 50 potential phytochemical compounds against a Spike glycoprotein of the wild-type and the Delta SARS-CoV-2 variant. Subsequently, molecular docking was performed for the five best compounds, such as Lupeol, Betulin, Hypericin, Corilagin, and Geraniin, along with synthetic controls. From the results obtained, it was evident that Lupeol exhibited a remarkable binding affinity towards the wild-type Spike protein (-8.54 kcal/mol), while Betulin showed significant binding interactions with the mutated Spike protein (-8.83 kcal/mol), respectively. The binding energy values of the selected plant compounds were slightly higher than that of the controls. Key hydrogen bonding and hydrophobic interactions of the resulting complexes were visualized, which explained their greater binding affinity against the target proteins-the Delta S protein of SARS-CoV-2, in particular. The lower RMSD, the RMSF values of the complexes and the ligands, Rg, H-bonds, and the binding free energies of the complexes together revealed the stability of the complexes and significant binding affinities of the ligands towards the target proteins. Our study suggests that Lupeol and Betulin could be considered as potential ligands for SARS-CoV-2 spike antagonists. Further experimental validations might provide new insights for the possible antiviral therapeutic interventions of the identified lead compounds and their analogs against COVID-19 infection.

Impact of COVID-19 Lockdown on Oral Oncology-related Outpatient Volume at Indian Dental Institutions.

AIM AND OBJECTIVE: This study aimed to evaluate the impact of the lockdown on oral oncology-related out-patient volume at Indian dental institutions. MATERIALS AND METHODS: The total number of newly diagnosed cases of oral submucous fibrosis, oral leukoplakia, oral lichen planus, and oral cancers, recorded at two dental institutional settings before lockdown (January-March 2020) and after lockdown (June-August 2020), were included retrospectively and compared. RESULTS: The study included a total of 797 cases at both institutions. At Institution-I, a total of 312 cases were recorded before the lockdown, and 63 cases were recorded after the lockdown. At Institution-II, a total of 311 cases were reported before lockdown, and 111 cases were recorded after lockdown. Comparisons between the pre-lockdown and post-lockdown data yielded a significant change in the proportions of oral sub-mucous fibrosis, oral leukoplakia, oral lichen planus, and oral cancers at both institutions (Chi-square test; p < 0.001). Following the lockdown, a substantial reduction was observed in the proportion of oral submucous fibrosis (OSMF) cases at both institutions, and the proportion of oral cancers increased at both institutions. There was a significant difference between the proportions of cases reported before lockdown at both institutions (p < 0.001). However, after-lockdown, no such differences were noted (p = 0.69); the absence of significance could most likely be due to the low sample size or low-power during the post-lockdown period. CONCLUSION: The oral potentially malignant disorders (OPMD) and oral cancer (OC) patient volumes reduced substantially following lockdown. During the post-lockdown period, the proportion of oral cancers increased, whereas the proportion of OSMF cases decreased. Results indicate that OPMD and oral cancer patients were impacted differently by the lockdown. CLINICAL SIGNIFICANCE: This study provides insight into the impact of lockdown and highlights the importance of reestablishing oral oncology-related patient care. A vital discussion is also provided on useful compensatory strategies that may reduce delays during the ongoing crisis. How to cite this article: Panta P, Reddy P, Misra SR, et al. Impact of COVID-19 Lockdown on Oral Oncology-related Outpatient Volume at Indian Dental Institutions. J Contemp Dent Pract 2021;22(5):501-505.

COVID-19 and Dentistry: An Updated Overview of Dental Perspectives and a Recommended Protocol for Dental Care and Emergency Dental Treatment.

AIM AND OBJECTIVE: This manuscript aims to provide an overview of the coronavirus disease-2019 (COVID-19) pandemic from dental perspectives, and presents standards and guidelines of dental care provision based on available research in this field as well as clinical experience and practice. BACKGROUND: The current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading around the globe and interferes with the provision of dental care for many individuals from different communities and backgrounds. A search for the literature on PubMed, ISI Web of Science, Scopus, EMBASE, and Cochrane Library from March 1, 2020 to December 30, 2020 was conducted. Also, the bibliographies included in the indicated articles were used to identify further literature. Recommendations by health authorities in different countries were also consulted. RESULTS: COVID-19 is causing many fatalities and is disrupting people's daily life and the economy in many countries around the world. Due to the potential of cross-infection through dental treatments, especially dental aerosol generation procedures, the dental profession has been disrupted during this pandemic. Dental care provision has been ceased completely or partially (limited to emergency or urgent treatment) in most countries around the world. Until this pandemic is controlled by new suitable treatments and/or vaccination, there is an urgent need to adopt immediate guidelines and standards for the safe provision of dental care to meet patients' demands, especially for the dental aerosols. CONCLUSION: Guidelines and standards for dental treatment amidst the COVID-19 pandemic are required. This manuscript provides an overview of the COVID-19 pandemic from dental perspectives and presents standards and guidelines of dental care provision based on available research in this field as well as clinical experience and practice. CLINICAL SIGNIFICANCE: This manuscript provides guidelines and standards for dental treatment and clinical management within dental settings amidst the COVID-19 pandemic, and resembles part of the quest to set the golden standards for dental care during the current circumstances. How to cite this article: AL-Omiri MK, Al-Shayyab MH, Al Nazeh AA, et al. COVID-19 and Dentistry: An Updated Overview of Dental Perspectives and a Recommended Protocol for Dental Care and Emergency Dental Treatment. J Contemp Dent Pract 2021;22(5):572-586.

COVID-19 and cardiovascular system-a comprehensive review.

Coronavirus disease 2019 (COVID-19), a mystified cryptic virus has challenged the mankind that has brought life to a standstill. Catastrophic loss of life, perplexed healthcare system and the downfall of global economy are some of the outcomes of this pandemic. Humans are raging a war with an unknown enemy. Infections, irrespective of age and gender, and more so in comorbidities are escalating at an alarming rate. Cardiovascular diseases, are the leading cause of death globally with an estimate of 31% of deaths worldwide out of which nearly 85% are due to heart attacks and stroke. Theoretically and practically, researchers have observed that persons with pre-existing cardiovascular conditions are comparatively more vulnerable to the COVID-19 infection. Moreover, they have studied the data between less severe and more severe cases, survivors and non survivors, intensive care unit (ICU) patients and non ICU patients, to analyse the relationship and the influence of COVID-19 on cardiovascular health of an individual, further the risk of susceptibility to submit to the virus. This review aims to provide a comprehensive particular on the possible effects, either direct or indirect, of COVID-19 on the cardiovascular heath of an individual.