Natural compounds as potential inhibitors of SARS-CoV-2 main protease: An in-silico study

Objective:To explore natural compounds as potential inhibitors against main protease (Mpro) of SARS-CoV-2. Methods:In the current study, systematic molecular docking analysis was conducted using AutoDock 4.2 to determine the binding affinities and interactions between natural compounds and Mpro. Selected natural compounds were further validated using a combination of molecular dynamic (MD) simulations and molecular mechanic Poisson-Boltzmann surface area (MM/PBSA) free energy calculations. Results:Out of twenty natural compounds, four natural metabolites namely, amentoflavone, guggulsterone, puerarin, and piperine were found to have strong interaction with Mpro of SARS-CoV-2 based on docking analysis. During MD simulations, all four natural compounds bound to Mpro at 50 ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands had stable and favorable energies with strong binding to Mpro protein. Conclusions:Guggulsterone is a potential inhibitor of COVID-19 main protease Mpro. Further in vitro and pre-clinical studies are needed.

Conservative management of an iliopsoas hematoma causing walking difficulty in an elderly patient on anticoagulation therapy: a case report

Spontaneous iliopsoas hematoma is a rare complication in patients suffering from bleeding disorders like hemophilia, Von Willebrand’s disease or those taking blood thinners like aspirin and clopidogrel or anticoagulant medications like warfarin for atrial fibrillation or post-thrombotic status. It can present as severe pain, muscle dysfunction, difficult walking or neurological dysfunction due to compression on femoral nerve or lumbar plexus. A high index of suspicion with early blood and radiological investigations like contrast enhanced computed tomography (CECT) or magnetic resonance imaging (MRI) of the part is immensely helpful in diagnosis and prompt management of such patients. A low hemoglobin or hematocrit level and a high INR is supportive while CECT or MRI of the abdomen and pelvis is confirmatory. Management in a hemodynamically and neurologically stable patient include immediate withdrawl of the anticoagulant, bed rest, infusion of I.V. fluids, vitamin K, fresh frozen plasma and packed red cell transfusion, which ensures complete recovery in most of the cases. However angio-embolization to control ongoing arterial bleeding is lifesaving when feasible or emergent open decompression and bleeding control surgery can save the life or prevent permanent neurological damage to the limb. Decompression of the hematoma by ultrasound or computed tomography guided catheter drainage is helpful alternative in few selected cases. We report an elderly patient on warfarin, who suddenly developed difficulty in walking within hours of a strained defecation, diagnosed to suffer from left iliopsoas hematoma and responded to conservative management with complete resolution of symptoms by 3 weeks.

Acute mesenteric venous thrombosis complicating endoscopic variceal sclerotherapy with absolute alcohol.

We report two patients, one with liver cirrhosis and another with extrahepatic portal vein obstruction, who developed acute mesenteric vein thrombosis following endoscopic variceal sclerotherapy with absolute alcohol. Both patients recovered after emergency laparotomy and resection of gangrenous bowel loop.