Overview of SARS-CoV-2 and Possible Targets for the Management of COVID-19 Infections

COVID-19 is a respiratory infection caused by a newer strain of coronavirus known as SARS-CoV-2. The major problem of COVID-19 infections is the ARDS, followed by respiratory failure, organ failure, and even death with multiple organ dysfunction, including cardiovascular collapse. Moreover, it affects the old age population with co-morbid conditions. The deficiency of diet, micronutrients, and vitamins also plays a key role in diminishing the immune power, and increases the rate of viral infectivity. The possible reasons and management methods are discussed in this review. The management methods enhance the host immune system via multi-functional and multi-targeted actions. The global rate of COVID-19 outbreak necessitates the need to develop newer medicines. The drug discovery process is based on the exposure of viral proteins, genome sequence, replication mechanisms, pathophysiological mechanisms, and host cell components (as a target) reactions. This article highlights the overview of coronavirus components, the replications process, and possible targets for the management of coronavirus infections. It may lead to the rapid development of newer medicines for the treatment of coronavirus in-fections.Copyright © 2022 Bentham Science Publishers.

Nanoemulsion as an Effective Inhibitor of Biofilm-forming Bacterial Associated Drug Resistance: An Insight into COVID Based Nosocomial Infections.

Antibiotic overuse has resulted in the microevolution of drug-tolerant bacteria. Understandably it has become one of the most significant obstacles of the current century for scientists and researchers to overcome. Bacteria have a tendency to form biofilm as a survival mechanism. Biofilm producing microorganism become far more resistant to antimicrobial agents and their tolerance to drugs also increases. Prevention of biofilm development and curbing the virulency factors of these multi drug resistant or tolerant bacterial pathogens is a newly recognised tactic for overcoming the challenges associated with such bacterial infections and has become a niche to be addressed. In order to inhibit virulence and biofilm from planktonic bacteria such as, Pseudomonas aeruginosa, Acinetobacter baumannii, and others, stable nanoemulsions (NEs) of essential oils (EOs) and their bioactive compounds prove to be an interesting solution. These NEs demonstrated significantly greater anti-biofilm and anti-virulence activity than commercial antibiotics. The EO reduces disease-causing gene expression, which is required for pathogenicity, biofilm formation and attachment to the surfaces. Essential NE and NE-loaded hydrogel surface coatings demonstrates superior antibiofilm activity which can be employed in healthcare-related equipments like glass, plastic, and metal chairs, hospital beds, ventilators, catheters, and tools used in intensive care units. Thus, anti-virulence and anti-biofilm forming strategies based on NEs-loaded hydrogel may be used as coatings to combat biofilm-mediated infection on solid surfaces.

Immune-mediated Acute Limb Ischemia: A Rare Complication of SARS-CoV-19 Infection

Occurrence of acute limb ischaemia (ALI) in patients with SARS-CoV-2 is an uncommon complication. COVID-19 has been associated with thrombotic disease secondary to a hypercoagulable state. COVID-19 appears to cause a hypercoagulable state through mechanisms unique to SARS-CoV-2 and centres on the cross-talk between thrombosis and inflammation. The proposed hypothesis includes a severely heightened inflammatory response that leads to thrombotic inflammation, through a mechanism such as cytokine storm, complement activation, and endothelitis. The innate and adaptive immune responses result in immunemediated thrombosis, leading to thrombotic complications, such as myocardial infarction, pulmonary embolism, deep vein thrombosis, and stroke. The activation of coagulation (D-dimer) and thrombocytopenia are important prognostic markers in SARSCoV- 19 infections. At our institution, we found six patients to have ALI and reviewed their characteristics and outcomes. Our findings showed that in severe COVID-19 disease, the association of ALI had high mortality. Materials and methods: It is a retrospective observational study performed at Bangalore Baptist hospital during the COVID-19 pandemic (August 2020 to August 2021). We report a case series of 6 ALI patients aged between 30 and 55 years. All the patients were tested positive for SARS-CoV-2 disease. All our patients received standard treatment care as per institution protocol for SARS-CoV-2 disease. They were all commenced on therapeutic anticoagulation at admission to ICU. Baseline coagulation profile and inflammatory markers and their trends were followed in all patients. The diagnosis of ALI in all ventilated patients was done clinically by the presence of pallor, pulselessness, acrocyanosis, blisters, and dry care unit with SARS-CoV-2 disease, 6 patients had developed limb ischemia (1.4%). Male and female preponderance was equal. Among 6 patients, 1 was newly detected diabetes mellitus, 2 were diabetic and hypertensive of which one had right upper limb post-polio paralytic sequelae, and the rest had no co-morbidities. The mean duration of ICU stay and mechanical ventilation days was 22 days and 17.8 days, respectively. All the patients had lower limb ischemia of which 3 were unilateral. Discoloration extended up to the ankle joint in almost all cases. As these patients were on the ventilator secondary to severe hypoxemia or vasopressor support, they were managed conservatively. Two patients presented with stroke, pyelonephritis with acute kidney injury, and septic shock requiring high vasopressor support. 5 of 6 patients died during the course of treatment (mortality 83%). All patients showed high inflammatory markers especially D-dimer during the initial development phase of limb ischemia. 1 survived patient required bilateral foot amputation due to dry gangrene. Conclusion: Limb ischemia with tissue necrosis is a dreadful complication and is associated with high mortality. High incidence of thrombosis despite therapeutic anticoagulation raises a question about pathophysiology unique to COVID-19. Evidence of inflammatory-mediated thrombosis and endothelial injury are possible explanations which would support the use of immunotherapy in addition to anticoagulation for the treatment of thrombotic events. Further insight into the cause and management of thrombosis is needed.

The Updated Review on Plant Peptides and Their Applications in Human Health.

Biologically active plant peptides, consisting of secondary metabolites, are compounds (amino acids) utilized by plants in their defense arsenal. Enzymatic processes and metabolic pathways secrete these plant peptides. They are also known for their medicinal value and have been incorporated in therapeutics of major human diseases. Nevertheless, its limitations (low bioavailability, high cytotoxicity, poor absorption, low abundance, improper metabolism, etc.) have demanded a need to explore further and discover other new plant compounds that overcome these limitations. Keeping this in mind, therapeutic plant proteins can be excellent remedial substitutes for bodily affliction. A multitude of these peptides demonstrates anti-carcinogenic, anti-microbial, anti-HIV, and neuro-regulating properties. This article's main aim is to list out and report the status of various therapeutic plant peptides and their prospective status as peptide-based drugs for multiple diseases (infectious and non-infectious). The feasibility of these compounds in the imminent future has also been discussed.

Anatomy teaching and learning in Malaysia during the COVID-19 pandemic

The abrupt transition from face-to-face to online anatomy teaching amidst the COVID-19 pandemic has posed great challenges to anatomy lecturers in Malaysia, as they have had to adapt to new skills to prepare and deliver online classes. These online classes were delivered either synchronously via a web teleconferencing application or asynchronously through pre-recorded videos that were uploaded to the learning management system (LMS). The online delivery of anatomy practical classes has become a major concern among anatomy lecturers and students, especially in public institutions, as there is a lack of hands-on experience and social interaction. Nevertheless, some private medical schools have adapted well to both online lectures and practical classes, as they had been venturing towards online learning and virtual reality tools even before the pandemic commenced. The Malaysian Anatomical Association (MAA) webinar, "Transformation of Anatomy Education in Malaysia during COVID-19 Pandemic", discussed the issues related to lecturers' and students' receptivity to online anatomy classes. This study discusses the issues related to online anatomy teaching and learning (T&L) and the actions taken by the university's governance and anatomy faculty members to resolve the issues discussed in the academic discourse. © 2021 Malaysian Association of Education in Medicine and Health Sciences and Penerbit Universiti Sains Malaysia.

Modelling studies reveal the importance of the C-terminal inter motif loop of NSP1 as a promising target site for drug discovery and screening of potential phytochemicals to combat SARS-CoV-2.

COVID-19 pandemic causative SARS-CoV-2 coronavirus is still rapid in progression and transmission even after a year. Understanding the viral transmission and impeding the replication process within human cells are considered as the vital point to control and overcome COVID-19 infection. Non-structural Protein 1, one among the proteins initially produced upon viral entry into human cells, instantly binds with the human ribosome and inhibit the host translation process by preventing the mRNA attachment. However, the formation of NSP1 bound Ribosome complex does not affect the viral replication process. NSP1 plays an indispensable role in modulating the host gene expression and completely steals the host cellular machinery. The full-length structure of NSP1 is essential for the activity in the host cell and importantly the loop connecting N and C-terminal domains are reported to play a role in ribosome binding. Due to the unavailability of the experimentally determined full-length structure of NSP1, we have modelled the complete structure using comparative modelling and the stability and conformational behaviour of the modelled structure was evaluated through molecular dynamics simulation. Interestingly, the present study reveals the significance of the inter motif loop to serves as a potential binding site for drug discovery experiments. Further, we have screened the phytochemicals from medicinal plant sources since they were used for several hundred years that minimizes the traditional drug development time. Among the 5638 phytochemicals screened against the functionally associated binding site of NSP1, the best five phytochemicals shown high docking score of -9.63 to -8.75 kcal/mol were further evaluated through molecular dynamics simulations to understand the binding affinity and stability of the complex. Prime MM-GBSA analysis gave the relative binding free energies for the top five compounds (dihydromyricetin, 10-demethylcephaeline, dihydroquercetin, pseudolycorine and tricetin) in the range of -45.17 kcal/mol to -37.23 kcal/mol, indicating its binding efficacy in the predicted binding site of NSP1. The density functional theory calculations were performed for the selected five phytochemicals to determine the complex stability and chemical reactivity. Thus, the identified phytochemicals could further be used as effective anti-viral agents to overcome COVID-19 and as well as several other viral infections.

SARS-CoV-2 genome diversity at the binding sites of oligonucleotides used for COVID-19 diagnosis (preprint)

ImportanceSARS-CoV-2 genomic variants impacts the overall sensitivity of COVID-19 diagnosis, leading to false-negative diagnosis and the continued spread of the virus. ObjectiveTo evaluate how nucleotide variability in target primer binding sites of the SARS-CoV-2 genomes may impact diagnosis using different recommended primer/probe sets, as well as to suggest the best primer/probes for diagnosis. DesignWe downloaded 105,118 public SARS-CoV-2 genomes from GISAID (Sept, 25th, 2020), removed genomes of apparent worst quality (genome length <29kb and/or >5% ambiguous bases) and missing metadata, and performed an analysis of complementarity for the 13 most used diagnostic primers/probe sets for RT-PCR detection. We calculated the N rate and % of genome recovery, with all primer/probe-sets considering viral origin and clade. Results: Our findings indicate that currently, the Paris_nCoV-IP2, -IP4 and WHO|E_Sarbeco primer/probe sets for COVID-19, to perform the best diagnostically worldwide, recovering >99.5% of the good quality SARS-CoV-2 genomes from GISAID, with no mismatches. The Chinese_CDC|2019-nCoV-NP primer/probe set, among the first to be designed during the pandemic, was the most susceptible to currently most abundant SARS-CoV-2 variants. Mismatches encompassing the binding sites for this set are more frequent in Clade-GR and are highly prevalent in over 30 countries globally, including Brazil and India, two of the hardest hit countries. Conclusions: Detection of SARS-CoV-2 in patients may be hampered by significant variability in parts of the viral genome that are targeted by some widely used primer sets. The geographic distribution of different viral clades indicates that continuous assessment of primer sets via sequencing-based surveillance and viral evolutionary analysis is critical to accurate diagnostics. This study highlights sequence variance in target regions that may reduce the efficiency of primer:target hybridization that in turn may lead to the undetected spread of the virus. As such, due to this variance, the Chinese_CDC|2019-nCoV-NP-set should be used with caution, or avoided, especially in countries with high prevalence of the GR clade. Key Points QuestionHow variable are the binding-sites of primers/probes used for COVID-19 diagnosis? FindingsWe investigated nucleotide variations in primer-binding sites used for COVID-19 diagnosis, in 93,143 SARS-CoV-2 genomes, and found primer sets targeting regions of increasingly nucleotide variance over time, such as the Chinese_CDC|2019-nCoV-NP. The frequency of these variations is higher in Clade-GR whose frequency is increasing worldwide. Paris_nCoV-IP2, IP4 and WHO|E_Sarbeco performed best. MeaningWe suggest the use of some sets to be halted and reinforce the importance of a continuous surveillance of SARS-CoV-2 variations to prompt the use of the best primers.