The chamber of secretome in Mycobacterium tuberculosis as a potential therapeutic target.

Mycobacterium tuberculosis (MTB) causes one of the ancient diseases, Tuberculosis, affects people around the globe and its severity can be understood by its classification as a second infectious disease after COVID-19 and the 13th leading cause of death according to a WHO report. Despite having advanced diagnostic approaches and therapeutic strategies, unfortunately, TB is still spreading across the population due to the emergence of drug-resistance MTB and Latent TB infection (LTBI). We are seeking for effective approaches to overcome these hindrances and efficient treatment for this perilous disease. Therefore, there is an urgent need to develop drugs based on operative targeting of the bacterial system that could result in both efficient treatment and lesser emergence of MDR-TB. One such promising target could be the secretory systems and especially the Type 7 secretory system (T7SS-ESX) of Mycobacterium tuberculosis, which is crucial for the secretion of effector proteins as well as in establishing host-pathogen interactions of the tubercle bacilli. The five paralogous ESX systems (ESX-1 to EXS-5) have been observed by in silico genome analysis of MTB, among which ESX-1 and ESX-5 are substantial for virulence and mediating host cellular inflammasome. The bacterium growth and virulence can be modulated by targeting the T7SS. In the present review, we demonstrate the current status of therapeutics against MTB and focus on the function and cruciality of T7SS along with other secretory systems as a promising therapeutic target against Tuberculosis.

Deciphering the immunogenic T-cell epitopes from spike protein of SARS-CoV-2 concerning the diverse population of India.

Scientists are rigorously looking for an efficient vaccine against the current pandemic due to the SARS-CoV-2 virus. The reverse vaccinology approach may provide us with significant therapeutic leads in this direction and further determination of T-cell/B-cell response to antigen. In the present study, we conducted a population coverage analysis referring to the diverse Indian population. From the Immune epitope database (IEDB), HLA- distribution analysis was performed to find the most promiscuous T-cell epitope out of In silico determined epitope of Spike protein from SARS-CoV-2. Epitopes were selected based on their binding affinity with the maximum number of HLA alleles belonging to the highest population coverage rate values for the chosen geographical area in India. 404 cleavage sites within the 1288 amino acids sequence of spike glycoprotein were determined by NetChop proteasomal cleavage prediction suggesting the presence of adequate sites in the protein sequence for cleaving into appropriate epitopes. For population coverage analysis, 179 selected epitopes present the projected population coverage up to 97.45% with 56.16 average hit and 15.07 pc90. 54 epitopes are found with the highest coverage among the Indian population and highly conserved within the given spike RBD domain sequence. Among all the predicted epitopes, 9-mer TRFASVYAW and RFDNPVLPF along with 12-mer LLAGTITSGWTF and VSQPFLMDLEGK epitopes are observed as the best due to their decent docking score and best binding affinity to corresponding HLA alleles during MD simulations. Outcomes from this study could be critical to design a vaccine against SARS-CoV-2 for a different set of populations within the country.Communicated by Ramaswamy H. Sarma.

Infodemics during era of COVID-19 pandemic: A review of literature.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread across the globe and has affected the health of millions of people. During the pandemic, social media was the major source of information for isolated and anxious people. Infodemics is defined as "an overburden of information - some accurate and some not - that makes it hard for people to find trustworthy source and reliable guidance when they need it." Misinformation raised out of infodemics during COVID-19 created many serious issues regarding the prevention and treatment of COVID-19. With the help of available literature, we aimed to review the role of infodemic in relation to worsening of COVID-19 spread and vaccine utilization with possible preventable measures to control infodemic. Various social media platforms were a major source of infodemic. The active role of world agencies, narrative guidelines by the local authority, use of artificial intelligence (AI) by social media platforms and active participation of community and health care professionals can control infodemics effectively.

Immunotherapeutic strategies to induce inflection in the immune response: therapy for cancer and COVID-19.

Cancer has agonized the human race for millions of years. The present decade witnesses biological therapeutics to combat cancer effectively. Cancer Immunotherapy involves the use of therapeutics for manipulation of the immune system by immune agents like cytokines, vaccines, and transfection agents. Recently, this therapeutic approach has got vast attention due to the current pandemic COVID-19 and has been very effective. Concerning cancer, immunotherapy is based on the activation of the host's antitumor response by enhancing effector cell number and the production of soluble mediators, thereby reducing the host's suppressor mechanisms by induction of a tumour killing environment and by modulating immune checkpoints. In the present era, immunotherapies have gained traction and momentum as a pedestal of cancer treatment, improving the prognosis of many patients with a wide variety of haematological and solid malignancies. Food supplements, natural immunomodulatory drugs, and phytochemicals, with recent developments, have shown positive trends in cancer treatment by improving the immune system. The current review presents the systematic studies on major immunotherapeutics and their development for the effective treatment of cancers as well as in COVID-19. The focus of the review is to highlight comparative analytics of existing and novel immunotherapies in cancers, concerning immunomodulatory drugs and natural immunosuppressants, including immunotherapy in COVID-19 patients.

Potential of phytocompounds from Brassica oleracea targeting S2-domain of SARS-CoV-2 spike glycoproteins: Structural and molecular insights.

By 24th Sep. 2021, there are more than 229 million COVID-19 cases worldwide, the researchers are tirelessly working to discover and develop an efficient drug molecule against this devastative viral infection. This study aims to evaluate the inhibitory efficiency of the organic acids and phenolic compounds present in Brassica oleracea (Tronchuda Cabbage) against spike glycoprotein in SARS-CoV-2. Thirty-seven phytocompounds are screened on the basis of their molecular weight (<500 g/mol) and 14 ligands are docked using Autodock Vina and Autodock4 (version 4.2.6). The stability of the top five docked complexes was analyzed using classical molecular dynamics (MD) simulation. ADMET analysis is performed for the top five compounds and their targets are identified using SwissTargetPrediction. Phytoactives from B. oleracea namely Astragalin, 3-p-coumaroylquinic acid, 4-p-coumaroylquinic acid and sinapoyl-D-glucoside showed high binding affinities and free energy of binding during molecular docking and MD simulation studies (∼ 8.5-9.0 kcal/mol) for the spike glycoprotein trimer of SARS-CoV2. The ADMET analysis revealed that these phytocompounds have good solubility in the aqueous phase and that they don't penetrate the blood brain barrier. Moreover, there is no P-gp substrate inhibition, CYP1A2 inhibition, CYP2C19 inhibition, CYP2C9 inhibition, CYP2D6 inhibition and CYP3A4 inhibition observed for these compounds. Additionally, zero PAINS alerts were reported. These findings from molecular docking and MD simulation studies suggest that astragalin and coumaroylquinic acids from Tronchuda cabbage possess potential inhibitory capacity against spike glycoprotein trimer of SARS-CoV-2 and could be further taken up as lead targets for drug discovery.

Adapting Policy Guidelines for Spine Surgeries During COVID-19 Pandemic in View of Evolving Evidences: An Early Experience From a Tertiary Care Teaching Hospital.

Introduction The recent novel coronavirus disease 2019 (COVID-19) pandemic has brought the world to a standstill. This outbreak not only affected healthcare systems but the resultant economic losses were also enormous. COVID-19 has demanded that the health care systems globally evolve, develop new strategies, identify new models of functioning, and at times, fall back on the old conservative methods of orthopedic care to decrease the risk of disease transmission. Although, the majority of hospitals are refraining from performing elective surgeries, emergent and urgent procedures cannot be delayed. Various strategies have been developed at the institute level to reduce the risk of infection transmission among the theatre team from an unsuspected patient (asymptomatic and presymptomatic) during the perioperative period. Material and methods The present study is a part of an ongoing project which is being conducted in a tertiary level hospital after obtaining research review board approval. All patients admitted either for vertebral fracture or spinal cord compression from February 2020 to May 2020 were included. The present study included 13 patients (nine males and four females) with an average age of 35.4 years The oldest patient was of 63 years which is considered a risk factor for developing severe COVID-19 infection.  Results Eight patients (61.5%) presented with spinal cord injury (SCI) due to vertebral fracture with fall from height (87.5%) as the most common etiology. Among the traumatic SCI patients, six (75%) were managed surgically with posterior decompression and instrumented fusion with pedicle screws while two patients (25%) were managed conservatively. There were four patients (30.8%) of tuberculosis of the spine of whom two (50%) were managed with posterior decompression, debridement, and stabilization with pedicle screws, samples for culture, biopsy, and cartridge-based nucleic acid amplification test (CBNAAT) were collected during the procedure; for the remaining two patients (50%), a trans-pedicular biopsy was performed to confirm the diagnosis for initiation of anti-tubercular therapy. Prolapsed intervertebral disc causing cauda equina syndrome was the reason for emergency surgery in one patient (7.7%). COVID-19 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription-polymerase chain reaction (RT-PCR) test was performed in four patients (30.8%), in whom the most common symptom was fever (two patients (50%)). These patients were residents of high prevalence area for COVID-19 infection. Sore throat (25%), fatigue (25%), and low oxygen saturation (25%) were present in one patient which prompted us to get the COVID-19 test. All patients were reported negative for COVID-19. Conclusion The structural organization and the management protocol we describe allowed us to reduce infection risk and ultimately hospital stay, thereby maximizing the already stretched available medical resources. These precautions helped us to reduce transmission and exposure to COVID-19 in health care workers (HCW) and patients in our institute. The aim of this article is that our early experience can be of value to the medical communities that will soon be in a similar situation.