Recent Advances in Machine Learning-Based Models for Prediction of Antiviral Peptides.

Viruses have killed and infected millions of people across the world. It causes several chronic diseases like COVID-19, HIV, and hepatitis. To cope with such diseases and virus infections, antiviral peptides (AVPs) have been applied in the design of drugs. Keeping in view the significant role in pharmaceutical industry and other research fields, identification of AVPs is highly indispensable. In this connection, experimental and computational methods were proposed to identify AVPs. However, more accurate predictors for boosting AVPs identification are highly desirable. This work presents a thorough study and reports the available predictors of AVPs. We explained applied datasets, feature representation approaches, classification algorithms, and evaluation parameters of performance. In this study, the limitations of the existing studies and the best methods were emphasized. Provided the pros and cons of the applied classifiers. The future insights demonstrate efficient feature encoding approaches, best feature optimization schemes, and effective classification techniques that can improve the performance of novel method for accurate prediction of AVPs.

A review on oral manifestations of COVID-19 disease.

COVID-19, a multi-system-affecting disease presents with an extensive clinical spectrum, ranging from no symptoms at all to fatal lung involvement. Several orofacial manifestations have also been reported, among which dysgeusia is one of the earliest reported symptoms. Several other manifestations of extensive variety have also been reported by various authors worldwide since the outbreak of the disease. This comprehensive review dispenses a synopsis of the orofacial manifestations of COVID-19 along with a working classification, the knowledge of which is of utmost importance to medical and dental professionals for early detection and prevention of transmission of the disease.

A review on oral manifestations of COVID-19 disease

COVID-19, a multi-system-affecting disease presents with an extensive clinical spectrum, ranging from no symptoms at all to fatal lung involvement. Several orofacial manifestations have also been reported, among which dysgeusia is one of the earliest reported symptoms. Several other manifestations of extensive variety have also been reported by various authors worldwide since the outbreak of the disease. This comprehensive review dispenses a synopsis of the orofacial manifestations of COVID-19 along with a working classification, the knowledge of which is of utmost importance to medical and dental professionals for early detection and prevention of transmission of the disease.

A study of rhino-orbito-cerebral mucormycosis with COVID-19: A new challenge in North West of Rajasthan.

Background: Mucormycosis is a life-threatening fungal disease in immunocompromised patients. There has been increase in the number of mucormycosis associated with COVID-19 patients in second wave. Now country battle with both COVID-19 and mucormycosis. An invasive mucormycosis infection has been a significant burden in India after COVID-19. It has been recently emerged a notifiable disease by the Rajasthan government. Our aim is to develop awareness regarding the importance of early detection and treatment of mucormycosis with COVID-19 and reduce the morbidity and mortality. Materials and Methods: This is a Prospective longitudinal study including 34 patients diagnosed with acute invasive fungal infection by contrast enhancement magnetic resonance imaging studies of paranasal, orbit and brain or nasal biopsy for KOH/culture. Diagnosis is made through routine blood tests, biopsy, and radiological imaging. The patients taken for the study were COVID-19 reverse transcription-polymerase chain reaction positive or recent post COVID-19 (within 15 days) or symptoms of COVID-19 with bilateral pneumonitis. The study was conducted with 34 patients admitted to the department of medicine with mucormycosis within a month may 2021. Results: A total of 34 patients with a mean age of 50.92 years old and male female ratio 24/10 (70.5/29.41) were included in this study. The most common comorbidity was diabetes mellitus (23 patients 67.64%). Nine patients were newly diagnosed or recent onset of diabetes with or after COVID-19 infection. Twenty-four (70.58%) patients were COVID-19 positive or recent (within 15 days) history of COVID-19 positive. Seven (20.58) patients had the history of steroid as a treatment during COVID-19 and 5 (14.70) patients was on oxygen inhalation. One (2.94%) patient was fully vaccinated, and 5 (14.70) patients had the history of steam inhalation. The most common involvement was naso-orbital mucormycosis found in 28 patients (82.35%) followed by nasal-and orbital 26 (76.47) and 18 (52.94), respectively. Naso-Orbito-Cerebral was seen in 16 (47.05) patients. The more common reported symptoms and signs were headache (76.47), facial numbness (64.70), Nasal discharge (52.94), and ophthalmoplegia (52.94). Cranial nerve involvement was seen in 10 patients (facial palsy in 8 patients and bulbar palsy in 2 patients). Total mortality was 7 (7/34 20.58%). Conclusion: COVID-19 infection associated with the wide range of invasive mucormycosis. Early diagnosis and Clinical suspicion of acute invasive fungal sinusitis among COVID-19 patients is essential for better outcomes and higher survival.

Résumé Contexte: La mucormycose est une maladie fongique mortelle chez les patients immunodéprimés. Il y a eu une augmentation du nombre de mucormycose associée aux patients Covid - 19 en deuxième vague. Maintenant, le pays se bat contre le Covid-19 et la mucormycose. Une infection invasive en mucormycose a été une charge significative en Inde après Covid - 19. Il a récemment émergé une maladie notifiable du gouvernement du Rajasthan. Notre objectif est de sensibiliser à l'importance de la détection et du traitement précoce de la mucormycose avec Covid-19 et de réduire la morbidité et la mortalité. Matériaux et méthodes: Il s'agit d'une étude longitudinale prospective comprenant 34 patients diagnostiqués avec une infection fongique invasive aiguë par un contraste d'imagerie magnétique des études d'imagerie par résonance magnétique de biopsie paranasale, en orbite et au cerveau ou nasale pour le KOH / la culture. Le diagnostic est posé par des tests sanguins de routine, une biopsie et une imagerie radiologique. Les patients pris pour l'étude ont été la réaction en chaîne de la transcription inverse de Covid-19, la réaction en chaîne de polymérase positive ou le post-COVID-19 récent (dans les 15 jours) ou les symptômes de Covid-19 avec une pneumonite bilatérale. L'étude a été menée avec 34 patients admis au Département de médecine avec mucormycose dans un mois en mai 2021. Résultats: Un total de 34 patients avec un âge moyen de 50,92 ans et un rapport féminine masculin 24/10 (70,5 / 29,41) ont été inclus dans cette étude. La comorbidité la plus courante était le diabète sucré (23 patients 67,64%). Neuf patients ont été récemment diagnostiqués ou un début récent du diabète avec ou après l'infection à Covid - 19. Vingt-quatre (70,58%) patients étaient des antécédents de Covid - 19 positifs ou récents (dans les 15 jours) de Covid - 19 positifs. Sept (20,58) patients avaient des antécédents de stéroïde comme traitement pendant les patients COVID-19 et 5 (14,70) étaient sous inhalation d'oxygène. Un patient (2,94%) a été entièrement vacciné et 5 (14,70) patients avaient des antécédents d'inhalation de vapeur. L'atteinte la plus courante était la mucormycose naso-orbitale trouvée chez 28 patients (82,35%), suivie respectivement par l'orbital nasal et orbital 26 (76,47) et 18 (52,94). Le naso - orbito-cervebral a été observé chez 16 (47,05) patients. Les symptômes et les signes rapportés les plus courants étaient des maux de tête (76,47), un engourdissement facial (64,70), une décharge nasale (52,94) et une ophtalmoplégie (52,94). Une atteinte du nerf crânien a été observée chez 10 patients (paralysie faciale chez 8 patients et paralysie bulbaire chez 2 patients). La mortalité totale était de 7 (7/34 20,58%). Conclusion: Infection Covid - 19 associée à la large gamme de mucormycose invasive. Le diagnostic précoce et la suspicion clinique de sinusite fongique invasive aiguë chez les patients COVID-19 sont essentiels pour de meilleurs résultats et une survie plus élevée. Mots-clés: Covid - 19, fongique, invasive, nasal, rhinocéros orbital cerebral.

Identification of prospective covalent inhibitors for SARS-CoV-2 main protease using structure-based approach.

The rapid global spread of SARS-CoV-2 has recently caused havoc and forced the world into a state of the pandemic causing respiratory, gastrointestinal, hepatic, and neurologic diseases. It persistently, through mutation, develops into new variants of the virus that have appeared over time. As main protease (Mpro) is involved in proteolysis of two overlapping polyproteins pp1a and pp1ab to produce 16 non-structural proteins having a paramount factor in the virus replication that have a cysteine-histidine catalytic dyad. A computational approach, guiding a covalent docking as it offers higher potency, long duration of action and decreased drug resistance advantages over the conventional docking of the ligands on a catalytic dyad, is applied for SARS-CoV-2 main protease (Mpro) in this manuscript to divulge better molecules. Mpro active site contains Cys145 residue which act as a nucleophile and can donate its electron to an electrophilic molecule by interacting covalently. Furthermore, the ligand-protein complexes are allowed to simulate their dynamic studies to look into their time-based interaction stability and also, a parallel study of ADME properties for the hit molecules is also performed. Important insights from the studies revealed that the interactions are persistent and molecules may be considered for further optimization in clinical investigation.Communicated by Ramaswamy H. Sarma.

Yogic Neti-Kriya Using Povidone Iodine: Can it have a Preventive Role Against SARS-CoV-2 Infection Gateway?

During this COVID-19 pandemic, except steroid, none of the therapeutic measures have showed any evidence of efficacy. Traditionally jala-neti using lukewarm salted water remains a yogic way of maintaining upper airway hygiene. Saline irrigation decreases the concentration of inflammatory mediators (e.g. histamine, leukotriene etc.) in nasal secretions, reduces the severity and frequency of sinusitis, reduce need of antibiotic therapy and restores competency of nasal mucosa. Jala-neti is an integral part of six cleansing techniques of yogic kriyas practised in India since thousands of years. Jala-neti can clean the upper airways, prevents colonization of infectious agents, removes foreign bodies, prevents stasis of mucous and subsequently enhances the drainage of paranasal sinuses and maintain health. Regular practice of Jala neti improves nasal symptoms and overall health status of patients with sinusitis. Jala-neti sample can even be used for COVID-19 diagnosis. Povidone iodine (PVP-I) has been utilized as a time tested antimicrobial agent with broad spectrum coverage against wide range of bacteria and viruses. Anti-SARS-CoV-2 action of PVP-I was seen at a concentration as low as 0.45%. PVP-I is generally well tolerated upto 5%, however nasal ciliotoxicity is reported at this concentration, however, this toxicity is not reported with lower concentrations(1.25% and 0.5%). So, theoretically, by using neti-kriya with povidone iodine (0.5-1%) as irrigation solution can combine and enhance the protection against COVID-19 and this can be an important armor in the fight against COVID-19. However, this hypothesis needs to be validated in real life clinical trial scenario before implementing.

Leukocytoclastic vasculitis as a cutaneous manifestation of ChAdOx1 nCoV-19 corona virus vaccine (recombinant).

With the present COVID-19 vaccination drive across the world, adverse skin reactions post COVID-19 vaccine is expected. Majority of these reactions seen were transient or local injection site reactions. However, as the larger population is being vaccinated, certain uncommon dermatological presentations including leukocytoclastic vasculitis, pityriasis rosea, and exacerbation of pre-existing autoimmune diseases are now being reported. Among all the COVID-19 vaccines, most of these reactions are seen with messenger ribonucleic acid-based Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273) vaccine. We report two cases of leukocytoclastic vasculitis following ChAdOx1 nCoV-19 corona virus vaccine (recombinant) that bring out potential new dermatological manifestations of recombinant corona virus vaccine being administered across the European, South American, and Asian countries. It is important for all health care workers and patients to be aware of the corona virus vaccine associated adverse cutaneous reactions.

A simple mathematical model to predict and validate the spread of Covid-19 in India.

The new outbreak of the corona virus (Covid-19) is expanding rapidly worldwide, disrupting millions and prompting authorities to take swift measures to avoid the disease. National lockdown imposed by the Indian government since 25 March 2020, the early lockdown action shows as compared to many other Countries/states can benefit from limiting the final size of the epidemic. A report on the issue of spreading the Covid-19 modeling in India is under review. This study analyzes Covid-19 infections by 20Dec 2021 and presents a mathematical approach for forecasting new cases or cumulative cases in practical situations. This forecast is much needed to schedule/continue medical set-ups for possible action to tackle the Covid-19 outbreak. It is important to mention here that the number of authors has proposed different models for predicting the expansion of Covid-19 to India and other countries; almost no model has yet to be demonstrated viable. With this mathematical model, it is simple to forecast the transfer of Covid-19. It is clear from the data that lockdown has played a significant role in controlling the transmission of the disease. A close match between the predicted empirical results and the available results proves the derived model similarity.

Experiences with use of a pulse oximeter multimodal device in outpatient management of children with Acute Respiratory Infection during Covid pandemic.

BACKGROUND: While Covid-19 infection rate in children is low, respiratory symptoms are a common mode of presentation which calls for better management of such symptoms. However, ARI case managemnet in primary health settings settings has challenges as health workers lack skills to count respiratory rate and check chest indrawing. To address this multimodal pulse oximeters have been introduced in health and wellness centres of seven states to ease the work of front line health workers. A study was undertaken to understand the usability of the multimodal pulse oximeter during Covid times. METHODS: A qualitative study was conducted with the aid of indepth interviews among a convenience sample of eleven health care workers from ten health and wellness centres. Interviews were conducted and recorded over phone, after obtaining consent. Transcribed interviews were coded and analysed on a qualitative analysis software. Content analysis was conducted. RESULTS: Total children screened during covid lockdown period (April 1-May 31) is 571, those diagnosed with pneumonia and severe pneumonia is 68 and 2. Health care workers were satisfied with pulse oximeter as it helped in timely diagnosis and treatment, and offered protection from possible infection as it mitigated the need for physical contact. CONCLUSION: The multimodal pulse oximeter is well accepted among providers as it is easy to use aiding in timely management of ARI in children. It has an added protection as it's use reduces the need for physical contact. It can be adopted in other HWC and primary health facilities.

Assessment of health infrastructure in tackling COVID-19: A case study of European and American scenario.

The COVID-19 coronavirus pandemic is an unparalleled threat intoday's quickly developing climate, and we face it as a global community. Like climate change, it is challenging our resilience from environmental health, social security, and government, to knowledge exchange and economic policy in all sectors of the economy and all fields of growth. So much as climate change, everybody's coming together would require the initiative. Throughout Europe and America, several organizations have mobilized to ensure that the neediest are not left behind, encouraging emergencies and disruptions avoidance and preparedness. The coronavirus outbreak has highlighted the growing community's strengths and vulnerabilities that it has influenced, and has provided us with the ability to benefit from each other's accomplishments and shortcomings. The comparison graph has also been shown in this paper displaying European and American scenarios. The globe might feel smaller amid disaster states and global travel bans, but it is a period when teamwork and looking outward were never more relevant.

Effect of nation-wide lock-down due to Covid-19 over industrial pollution in Delhi, India.

In India, very first infection due to Covid-19 was reported by end of January 2020 and, the same has been increased with the span of time. In order to fight the increasing risk among the citizens of nation, the complete lock-down was declared on March 25, 2020 for initially 21 days and thereafter it has been subsequently increased up to its present 4th phase, which would be remain continue until May 31, 2020. First two phases of lock-down were imposed without any relaxation, however, there were gradual relaxation implemented in third and fourth lock-down phases. Air pollution depends on emission of the pollutants from vehicles and industries, as well as dust from construction activities. Due to lock-down, operations concerning these activities were completely shut down. The effect of lock-down on PM2.5, PM10, NO2, SO2, CO and AQI level was studied and comparison of PM2.5, PM10, NO2, SO2, CO and AQI during lock-down with same dates of previous year was also considered.

Stem cell therapy in COVID-19: Pooled evidence from SARS-CoV-2, SARS-CoV, MERS-CoV and ARDS: A systematic review.

BACKGROUND: SARS-CoV-2, which majorly affects the lungs and respiratory tract is thought due to dysregulation of the immune system which causes an immense imbalance of the cytokines. However, till now no standard treatment has been developed in treating the disease. On the other hand, it becomes important to prevent the acute respiratory tract infection due to COVID-19 which is the most dangerous phase leading to increased mortality. Hence this systematic review has been framed by pooling the available data of the use of stem cells in SARS-CoV-2, SARS-CoV, MERS-CoV and ARDS. METHODS: 6 literature databases (PubMed, EMBASE, Scopus, Google Scholar, Clinicaltrials.gov, and Clinical trial registry of India) were searched for relevant studies till 10th August 2020 using keywords stem cells, mesenchymal stem cells, cell therapy, SARS CoV-2, SARS Coronavirus, Coronavirus 2, COVID-19, nCoV-19, Novel Coronavirus, MERS CoV, ARDS, acute respiratory distress syndrome. RESULTS: The observations of this systematic review suggest capability of MSCs in reducing the systemic inflammation and protecting against SARS-CoV-2 as evidenced by the available clinical data. CONCLUSION: MSCs can overcome the clinical challenges currently faced by SARS-CoV-2 infected patients, specifically who are seriously ill and not responding to conventional therapies. Though the available clinical data is motivating, still predicting the therapeutic potential of MSCs will be too early in COVID-19. Hence, further studies in a larger cohort of patients becomes a prerequisite to validate their potential efficacy.

Additive Manufacturing Enabled Supply Chain in Combating COVID-19

Additive manufacturing (AM) is a method in which three-dimensional structures are successively laid down to create a solid object. The inherent advantages of AM technology are successfully drafted and exploited by the different organization across the globe. During the time of pandemic i.e. COVID-19, 3D printing has come to rescue and has been used for manufacturing critical medical supplies. 3D printing has been used in manufacturing some of the critical items like ventilators valves, face shields, swabs, oxygen valves, hand sanitizer holders, 3-DP lung models, etc. The main reason for its success has been the ability of 3D printing to print locally by using digital designs and thus reducing the number of supply chain actors. Also, the ability of 3D printing to manufacture/print complex geometrical designs locally is the main reason for its successful adoption during COVID-19. In this paper, we have discussed how AM has come to the forefront in fighting this pandemic. Various AM techniques have played a critical role in bridging the supply chain gap in the medical industry and locally printing critical devices. There were certain apprehensions before the pandemic along with slow adoption but this pandemic has also increased the adoption of AM due to its ability to overcome the demand created by COVID-19.

Application of additive manufacturing in challenges posed by COVID-19.

COVID-19 has brought a lot of turbulence and instability among manufacturing organizations. This pandemic has affected all three types of manufacturing operations- subtractive, additive and forming manufacturing processes. In this paper we have discussed how additive manufacturing has played a role in this time of crisis. There has been an increased adoption of additive manufacturing to overcome the demand created by this pandemic. The number of actors in additive supply chain have reduced and thus in the time of epidemics that has been a boom and has helped manufacturers relying on additive manufacturing to be agile and react in nearly no time to the requirements. The same has been found its use primarily in manufacturing healthcare facilities in short notices along with producing parts of medical equipment like ventilators.

Molecular diagnosis of COVID-19 in different biologic matrix, their diagnostic validity and clinical relevance: A systematic review.

Due to COVID 19 outbreak many studies are being conducted for therapeutic strategies and vaccines but detection methods play an important role in the containment of the disease. Hence, this systematic review aims to evaluate the effectiveness of the molecular detection techniques in COVID-19. For framing the systematic review 6 literature databases (PubMed, EMBASE, OVID, Web of Science, Scopus and Google Scholar) were searched for relevant studies and articles were screened for relevant content till 25th April 2020. Observations from this systematic review reveal the utility of RT-PCR with serological testing as one such method cannot correlate with accurate results. Availability of point of care devices do not conform to sensitivity and specificity in comparison to the conventional methods due to lack of clinical investigations. Pivotal aim of molecular and serological research is the development of detection methods that can support the clinical decision making of patients suspected with SARS-CoV-2. However, none of the methods were 100% sensitive and specific; hence additional studies are required to overcome the challenges addressed here. We hope that the present article with its observations and suggestions will assist the researchers to realize this vision in future.

Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: A systematic review and meta-analysis.

Following the demonstration of the efficacy of hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 in vitro, many trials started to evaluate its efficacy in clinical settings. However, no systematic review and meta-analysis have addressed the issue of the safety and efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019. We conducted a systematic review and meta-analysis with the objectives of evaluation of safety and efficacy of HCQ alone or in combination in terms of "time to clinical cure," "virological cure," "death or clinical worsening of disease," "radiological progression," and safety. RevMan was used for meta-analysis. We searched 16 literature databases out of which seven studies (n = 1358) were included in the systematic review. In terms of clinical cure, two studies reported possible benefit in "time to body temperature normalization" and one study reported less "cough days" in the HCQ arm. Treatment with HCQ resulted in less number of cases showing the radiological progression of lung disease (odds ratio [OR], 0.31, 95% confidence interval [CI], 0.11-0.9). No difference was observed in virological cure (OR, 2.37, 95% CI, 0.13-44.53), death or clinical worsening of disease (OR, 1.37, 95% CI, 1.37-21.97), and safety (OR, 2.19, 95% CI, 0.59-8.18), when compared with the control/conventional treatment. Five studies reported either the safety or efficacy of HCQ + azithromycin. Although seems safe and effective, more data are required for a definitive conclusion. HCQ seems to be promising in terms of less number of cases with radiological progression with a comparable safety profile to control/conventional treatment. We need more data to come to a definite conclusion.

In-silico homology assisted identification of inhibitor of RNA binding against 2019-nCoV N-protein (N terminal domain).

The N terminal domain (NTD) of Nucleocapsid protein (N protein) of coronavirus (CoV) binds to the viral (+) sense RNA and results in CoV ribonucleoprotien (CoV RNP) complex, essential for the virus replication. In this study, the RNA-binding N terminal domain (NTD) of the N protein was targeted for the identification of possible inhibitors of RNA binding. Two NTD structures of N proteins were selected (2OFZ and 1SSK, 92% homology) for virtual screening of 56,079 compounds from Asinex and Maybridge library to identify top 15 hits for each of the targets based on 'docking score'. These top-hits were further screened for MM-GBSA binding free energy, pharmacokinetic properties (QikProp) and drug-likeness (SwissADME) and subjected to molecular dynamics (MD) studies. Two suitable binders (ZINC00003118440 and ZINC0000146942) against the target 2OFZ were identified. ZINC00003118440 is a theophylline derivative under the drug class 'bronchodilators' and further screening with approved bronchodilators was also studied to identify their ability to bind to the RNA binding region on the N protein. The other identified top hit is ZINC0000146942, which is a 3,4dihydropyrimidone class molecule. Hence this study suggests two important class of compounds, theophylline and pyrimidone derivaties as possible inhibitors of RNA binding to the N terminal domain of N protein of coronavirus, thus opening new avenues for in vitro validations. Communicated by Ramaswamy H. Sarma.

Drug targets for corona virus: A systematic review.

The 2019-novel coronavirus (nCoV) is a major source of disaster in the 21th century. However, the lack of specific drugs to prevent/treat an attack is a major need at this current point of time. In this regard, we conducted a systematic review to identify major druggable targets in coronavirus (CoV). We searched PubMed and RCSB database with keywords HCoV, NCoV, corona virus, SERS-CoV, MERS-CoV, 2019-nCoV, crystal structure, X-ray crystallography structure, NMR structure, target, and drug target till Feb 3, 2020. The search identified seven major targets (spike protein, envelop protein, membrane protein, protease, nucleocapsid protein, hemagglutinin esterase, and helicase) for which drug design can be considered. There are other 16 nonstructural proteins (NSPs), which can also be considered from the drug design perspective. The major structural proteins and NSPs may serve an important role from drug design perspectives. However, the occurrence of frequent recombination events is a major deterrent factor toward the development of CoV-specific vaccines/drugs.