Anti-COVID-19 terpenoid from marine sources: A docking, admet and molecular dynamics study.

Traditional medicines contain natural products (NPs) as main ingredient which always give new direction and paths to develop new advanced medicines. In the COVID-19 pandemic, NPs can be used or can help to find new compound against it. The SARS coronavirus-2 main protease (SARS CoV-2 Mpro) enzyme, arbitrate viral replication and transcription, is target here. The study show that, from the electronic features and binding affinity of all the NPs with the enzyme, the compounds with higher hydrophobicity and lower flexibility can be more favorable inhibitor. More than fifty NPs were screened for the target and one terpenoid (T3) from marine sponge Cacospongia mycofijiensis shows excellent SARS CoV-2 Mpro inhibitory activity in comparison with known peptide based inhibitors. The molecular dynamics simulation studies of the terpenoids with the protein indicates that the complex is stable and hydrogen bonds are involved during the complexation. Considering binding affinity, bioavailability, pharmacokinetics and toxicity of the compounds, it is proposed that the NP T3 can act as a potential drug candidate against COVID-19 virus.

Identification of 4-acrylamido-N-(pyridazin-3-yl)benzamide as anti-COVID-19 compound: a DFTB, molecular docking, and molecular dynamics study.

Omicron is one of the variants of COVID-19 and continuing member of a pandemic. There are several types of vaccines that were developed around the globe to fight against the virus. However, the world is suffering to find suitable drug candidates for the virus. The main protease (Mpro) enzyme of the virus is the best target for finding drug molecules because of its involvement in viral infection and protein synthesis. ZINC-15 is a database of 750 million commercially available compounds. We find 125 compounds having two aromatic rings and amide groups for non-covalent interactions with active site amino acids and functional groups with the capability to bind -SH group of C145 of Mpro through covalent bonding by a nucleophilic addition reaction. The lead compound (Z144) was identified using molecular docking. The non-covalent interactions (NCI) calculations show the interactions between amino acids present in the active site of the protein and the lead molecules are attractive in nature. The density functional-based tight-binding (DFTB) study of the lead compound with amino acids in the active site indicates that Q190 and Q193 play a very critical role in stabilization. The Michael addition of the acrylamide group of the lead molecule at ß-position is facile because the low energy lowest unoccupied molecular orbital (LUMO) is concentrated on the group. From molecular dynamics during 100 ns, it has come to light that strong non-covalent interactions are key for the stability of the lead inside the protein and such binding can fold the protein. The free energy for this interaction is -42.72 kcal mol-1 which was obtained from MM-GB/SA calculations.

Global impacts of pre- and post-COVID-19 pandemic: Focus on socio-economic consequences.

On March 11, 2020, the novel Corona virus disease (COVID-19), was described as a pandemic by World Health Organization (WHO). Globally, the COVID-19 has not only affected the public health socially but also has rigorously affected economically. Substantial declines in income, increase in unemployment, and distractions in the transportation, amenities, and industrial sectors are amongst the major concerns of the pandemic disease extenuation. Furthermore, the governments of most of the countries underestimated the menaces of COVID-19 spread and were typically responsive for the calamities in their respective countries. As outbreak of this pandemic is not likely to wane in the nearby future, preventive actions are prerequisite to prevent infection spread, save people lives and also to save the economic affluence. In this review, based on the present knowledge and available literature, we have demonstrated the various aspects of pre-and post-COVID-19 effects over the social and economic phases worldwide. Moreover, the evidence based data have been summarized regarding threats, social influences, scientific upgrades, moral dynamics, stress and adapting in the pre- and post- COVID-19 situations.

Molecular designing, crystal structure determination and in silico screening of copper(II) complexes bearing 8-hydroxyquinoline derivatives as anti-COVID-19.

The pandemic by COVID-19 is hampering everything on the earth including physical and mental health, daily life and global economy. At the moment, there are no defined drugs, while few vaccines are available in the market to combat SARS-CoV-2. Several organic molecules were designed and tested against the virus but they did not show promising activity. In this work we designed two copper complexes from the ligands analogues with chloroquine and hydroxychloroquine. Both the ligands and complexes were well characterized by using various spectroscopic, thermal and X-ray diffraction techniques. Both the complexes as well as ligands were screened through in silico method with the chloroquine and hydroxychloroquine which essentially proved pivotal for successful understanding towards the target protein and their mechanism of action. The results indicated that the balanced hydrophobic and polar groups in the complexes favor their binding in the active site of the viral ADP-ribose-1 monophosphatase enzyme over the parent organic molecules.

Persistent Hypokalemia post SARS-coV-2 infection, is it a life-long complication? Case report.

INTRODUCTION AND IMPORTANCE: SARS-CoV-2 is a novel infection that has affected millions of people around the world. Complications of the infection may affect multiple systems including cardiovascular, neurological, gastrointestinal, urinary, and pulmonary systems. Hypokalemia, which is a life-threatening condition that may lead to arrhythmia and possibly death, has been noticed in more than half of the COVID-19 patients. Further understanding of the disease process and its complications is necessary to guide in preventing the complications from happening in the first place and finding treatment for patients with an already established complications. CASE PRESENTATION: A 34-year old male from Philippines who lives in Saudi Arabia - Riyadh and works as health care provider with no previous history of any medical illness. Presented by himself to the emergency department (ED) with dry cough, shortness of breath, fever, malaise, and fatigability for five days. On examination (RR 25), (T 38.6 °C) and (O2 89% Room air), on auscultation there was a decrease on air entry bilaterally with scattered crepitations, no wheezing or stridor. Covid-19 swab was positive, (Day 1) potassium 2.91 (mmol/L) magnesium (mmol/L) with normal baseline before getting infected. CLINICAL DISCUSSION: Patient while in the hospital was on daily potassium oral and IV replacement with IV magnesium replacement. Investigation showed 24Hr urine potassium 47.3 (mmol/L), 24Hr urine magnesium 5.52 (mmol/L), 24Hr urine Creatinine 9.25 (mmol/L), (TTKG) Transtubular Potassium Gradient 18 and (VBG) PH:7.38, Pco2:44 (mmHg) Po2:55 (mmHg) HCO3:25 (mEq/L). Patient has an increased renal potassium loss with normal VBG on separate days and normal Blood pressure that excludes diseases with associated acidemia or alkalemia. Our patient didn't want to go for any invasive diagnostic procedures and favored to wait for spontaneous recovery. CONCLUSION: We followed up the potassium level of our patient for more than 5 months since he was diagnosed with COVID-19 to find out that he is still having hypokalemia, as well as, hypomagnesemia. Long term complications of COVID-19 infection such as hypokalemia and hypomagnesemia need to be observed and followed up closely to avoid life-threatening arrythmias and seizures. The attention of the scientific community to possible long term or permanent complications is needed to help find preventive measures and treatment for patients with complications.