SARS‑CoV‑2 infection and children: Insights from the 6th Workshop on Paediatric Virology (Review)

The present article provides an overview of the key messages of the plenary lectures on severe acute respira‑ tory syndrome coronavirus type 2 (SARS‑CoV‑2) infection in children, which were presented at the ‘6th Workshop on Paediatric Virology' organised by the Institute of Paediatric Virology on October 24, 2020. SARS‑CoV‑2 is a novel © 2021 Polish Otolaryngology Society. All rights reserved.

Clinical manifestation and impact on management of acute coronary syndrome during covid-19 pandemic, lessons learnt from a tertiary care

Funding Acknowledgements Type of funding sources: None. Introduction The World Health Organization first characterized COVID-19 as a ongoing pandemic since  12th March 2020. Since then, mitigation plans including vaccinations are on the run globally. During this pandemic several restrictions worldwide are being followed , which had major impact on acute coronary syndrome presentation due to various factors.At our tertiary cardiac care centre we analyzed the consecutive acute coronary syndrome admissions and its impact in the management during the pandemic lockdown . Purpose Our study aimed in identifying the salient clinical manifestations and impact on the management of Acute Coronary Syndrome (ACS) during the 1st wave of COVID-19 Pandemic in a tertiary care center to inform future implications/preparedness for ACS care during the revolving Pandemic. Methods Clinical profile of patients admitted in our tertiary coronary care unit between March – June 2020 was analyzed. Descriptive statistics was performed, and continuous data were reported as mean ± SD and as percentages. Results Among the consecutive 265 patients who were treated in our coronary care unit, mean age of the patients was 58.43 ± 11.366 years and about 81% of them were males. Nearly one third of the patients presented with non-ST elevation MI at the time of diagnosis. Previous history of MI was well pronounced in 63% (N = 169) of the patients with a combined history of hypertension, diabetes, dyslipidemia. A higher proportion of patients presented with mild to moderate left ventricular dysfunction (N = 123, 46.6%). Higher rates of patients needed thrombolysis care (68%) where thrombolysis with ELAXIM (N = 41), STK (N = 22) were commonly used in the process. About 96.2% of the patients presented with delayed window period of >48 hours and about 75% of them underwent ADHOC PCI procedure as the next level of management during admission.  Coronary angiogram findings were suggestive of a triple vessel disease in 36% of the patients with previous history of coronary interventions with in the last 5 years. Complications of cardiogenic shock requiring IABP(N = 5). and death were very minimal and were seen in patients with previous coronary bypass surgery with in last 5 years (died, N = 2), acute pulmonary thromboembolism (IABP, N = 2) . Conclusion We observed patients with late presentation to hospital, covid protocol has increased thrombolysis compared to primary PCI in non covid time with no major bleeding risks in our patients .Most of our patients opted for ADHOC PCI ,  preexisting coronary artery disease patients presented as triple vessel disease .Though late presentation no significant complication rate noted.Further study would facilitate healthcare planning and preparedness for further COVID waves.

In silico Studies Predict Efficient Binding of Remdesivir and Favipiravir with 3-chymotrypsin like protease of SARS-CoV-2 for COVID-19 Interventional Therapy

Favipiravir and remdesivir are investigational drugs for coronavirus disease 2019 that is caused by severe acute respiratory syndrome coronavirus 2. The active forms of these drugs are reported to target and inhibit viral RNA dependent RNA polymerase, which is derived from 3-chymotrypsin like protease, a viral replicase enzyme. The present in silico study explores the comparative efficacy of these drugs to inhibit 3-chymotrypsin like protease and RNA dependent RNA polymerase, to plan therapeutic options for patients based on their disease severity. Active favipiravir and remdesivir molecules bind to 3-chymotrypsin like protease with energies of 6.18 and -6.52 kcal/mol in contrast to -5.62 and -3.91 kcal/mol for RNA dependent RNA polymerase. Further, hydrophobic interactions and salt bridge formations cement drug bindings with 3-chymotrypsin like protease, but not with RNA dependent RNA polymerase. Molecular dynamic simulation experiments, performed under certain experimental constraints reveal that the root mean square flexibilities of active residues in drug complexes with 3-chymotrypsin like protease are lower than in free 3-chymotrypsin like protease making the former more stable than the latter because of their rigidity and stabilities. Both drugs may hence serve as good therapeutic options for early stages of coronavirus disease 2019. However, more severe symptoms may be treated better with favipiravir due to its better binding with RNA dependent RNA polymerase, as compared to remdesivir. The "one drug does not fit all" concept is true for coronavirus disease 2019 as it is being currently realized by clinicians all around the world. Hence precise knowledge about critical interactions of these drugs with the viral enzymes will help medicos make vital therapeutic decisions on interventional options for patients who report to hospitals without over symptoms or with varying degrees of disease severity.

Therapeutic Phytochemical Actives for Potential Control of SARS-CoV-2

Background: Drug development strategies for treating COVID-19 focus on actives that either physically block angiotensin-converting enzyme-2 (ACE-2) receptors (viral entry point), or those, which inactivate viral proteases like 3CLpro or RdRp, inside the infected host cells. Objectives: The objective of the present study is to virtually screen phytochemicals for both these purposes. Methods: Molecular docking, molecular dynamic simulation (MDS) and multiple sequence alignment were employed. Results: All the screened phytochemical actives showed negative binding energies with their respective targets, attesting good complex stabilities. Among each set of ten actives, for blocking ACE-2 receptors and for inactivation of 3CLpro and RdRp, Dichamanetin-ACE-2, Glabrene-3CLpro and Naringenin-RdRp complexes were most stable, with binding energies of -9.8, -9.11 and -7.7 Kcal/mol respectively. MDS studies of these representative actives and their complexes, also attested to complex stabilities. Multiple sequence alignment analysis of nine significant amino acid residues of the Homo sapiens ACE-2 receptor, with nine different species, showed conservation of several residues. Conclusion: A set of phytochemicals actives can block ACE-2 receptors and prevent the entry of SARS-CoV-2 into host endothelial cells. Two other sets of actives can inactivate viral 3CLpro and RdRp enzymes and prevent replication of SARS-CoV-2 inside host cells. They all can hence be further explored for the control of COVID-19.