The impact of calcitriol and estradiol on the SARS-CoV-2 biological activity: a molecular modeling approach

The novel coronavirus disease (COVID-19) is currently a big concern around the world. Recent reports show that the disease severity and mortality of COVID-19 infected patients may vary from gender to gender with a very high risk of death for seniors. In addition, some steroid structures have been reported to affect coronavirus, SARS-CoV-2, function and activity. The entry of SARS-CoV-2 into host cells depends on the binding of coronavirus spike protein to angiotensin converting enzyme-2 (ACE2). Viral main protease is essential for the replication of SARS-CoV-2. It was hypothesized that steroid molecules (e.g., estradiol, progesterone, testosterone, dexamethasone, hydrocortisone, prednisone and calcitriol) could occupy the active site of the protease and could alter the interaction of spike protein with ACE2. Computational data showed that estradiol interacted more strongly with the main protease active site. In the presence of calcitriol, the binding energy of the spike protein to ACE2 was increased, and transferring Apo to Locked S conformer of spike trimer was facilitated. Together, the interaction between spike protein and ACE2 can be disrupted by calcitriol. Potential use of estradiol and calcitriol to reduce virus invasion and replication needs clinical investigation.

Molecular Docking and Molecular Dynamics Studies of Role of Anti-Allergic Medicines as Inhibitors Against Covid-19

The 2019-nCoV virus is a human-infectious coronavirus (CoV). Very few treatment options are available to healthcare professionals who are fighting this outbreak at the front. The main warning symptoms of COVID-19, the disease caused by the new coronavirus, are fever, fatigue, and a dry cough, sometimes it also causes cold-like symptoms like a runny nose which are sometimes similar to symptoms of allergies and sometimes difficult to differentiate between COVID-19 and allergies. The anti-allergic drug molecules can behave as good inhibitor against COVID-19. Molecular docking studies have been performed to examine the inhibitor properties of anti-allergic molecules against Covid-19. The searching of better inhibitors have been examined interns of various non-covalent interactions like hydrogen bond, halogen bond, vander waal’s interactions, alkyl-πand π-π interactions between small molecules (Anti-allergic medicines) with main protease of Covid-19 using molecular docking and Molecular Dynamics simulation which reveals that astemizole is best inhibitor among ten Anti-allergic drug molecules.

Malonic Acid-Type Fullerene Derivatives Strongly Inhibit The SARS-Cov-2 Main Protease

COVID-19 is a disease that is causing a global pandemic. There is an urgent need to develop new drugs to treat it. In this study, we evaluated the inhibitory activities of a series of fullerene derivatives against the main protease of SARS-CoV-2, the virus that causes COVID-19. As a result, it was found that the malonic acid-type fullerene derivatives showed strong inhibitory activities.

Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2

The worldwide COVID-19 pandemic caused by the coronavirus SARS-CoV-2 urgently demands novel direct antiviral treatments. The main protease (Mpro) and papain-like protease (PLpro) are attractive drug targets among coronaviruses due to their essential role in processing the polyproteins translated from the viral RNA. In the present work, we virtually screened 688 naphthoquinoidal compounds and derivatives against Mpro of SARS-CoV-2. Twenty-four derivatives were selected and evaluated in biochemical assays against Mpro using a novel fluorogenic substrate. In parallel, these compounds were also assayed with SARS-CoV-2 PLpro. Four compounds inhibited Mpro with half-maximal inhibitory concentration (IC50) values between 0.41 μM and 66 μM. In addition, eight compounds inhibited PLpro with IC50 ranging from 1.7 μM to 46 μM. Molecular dynamics simulations suggest stable binding modes for Mpro inhibitors with frequent interactions with residues in the S1 and S2 pockets of the active site. For two PLpro inhibitors, interactions occur in the S3 and S4 pockets. In summary, our structure-based computational and biochemical approach identified novel naphthoquinonal scaffolds that can be further explored as SARS-CoV-2 antivirals.