A MOLECULAR DOCKING STUDY: TARGETING COVID-19 (SARS-COV-2) MAIN PROTEASE USING ACTIVE PHYTOCOMPOUNDS FROM TERMINALIA ARJUNA

Objective: COVID-19 is transmissible disease triggered by SARS-CoV-2 strain of coronavirus family. It infected a million of people worldwide. Hence, an attempt was made to identify natural compounds from Terminalia arjuna, having multiple medicinal values in Indian Ayurveda, to prevent the disease, using molecular docking, drug likeness prediction and ADME analysis. Methods: SARS-CoV-2 main protein was retrieved from the PDB database. The ligands with poor binding and molecules that can affect docking were removed and docking is done with PyRx tool. ADME and drug likeness analysis were done using Swiss-ADME and Admetlab web server. Results: Ramachandran plot analysis shows the statistical distribution of the combinations of the backbone dihedral angles ϕ and ψ of the protein. Molecular docking studies show five compounds from T. arjuna, which have potential binding affinity to resist the main protease Mpro by preventing proteolytic cleavage, translation, and replication of virus. ADMET profile and drug likeness prediction showed that, among these five compounds Triterpenoid and N-Desmethyl Sildenafil were safe and possess the drug-like properties. Conclusion: The present study suggests that Triterpenoid and N-Desmethyl Sildenafil have specific binding affinity and they could inhibit main protease Mpro and also helps to manage the therapeutic strategies against COVID-19

Operator theory on generalized Hartogs triangles

We consider the family $\mathcal P$ of $n$-tuples $P$ consisting of polynomials $P_1, \ldots, P_n$ with nonnegative coefficients which satisfy $\partial_i P_j(0) = \delta_{i, j},$ $i, j=1, \ldots, n.$ With any such $P,$ we associate a Reinhardt domain $\triangle^{\!n}_{_P}$ that we will call the generalized Hartogs triangle. We are particularly interested in the choices $P_a = (P_{1, a}, \ldots, P_{n, a}),$ $a \geq 0,$ where $P_{j, a}(z) = z_j + a \prod_{k=1}^n z_k,~ j=1, \ldots, n.$ The generalized Hartogs triangle associated with $P_a$ is given by \begin{equation} \triangle^{\!n}_a = \Big\{z \in \mathbb C \times \mathbb C^{n-1}_* : |z_j|^2 < |z_{j+1}|^2(1-a|z_1|^2), ~j=1, \ldots, n-1, |z_n|^2 + a|z_1|^2 < 1\Big\}. \end{equation} The domain $\triangle^{\!n}_{_P},$ $n \geq 2$ is never polynomially convex. However, $\triangle^{\!n}_{_P}$ is always holomorphically convex. With any $P \in \mathcal P$ and $m \in \mathbb N^n,$ we associate a positive semi-definite kernel $\mathscr K_{_{P, m}}$ on $\triangle^{\!n}_{_P}.$ This combined with the Moore's theorem yields a reproducing kernel Hilbert space $\mathscr H^2_m(\triangle^{\!n}_{_P})$ of holomorphic functions on $\triangle^{\!n}_{_P}.$ We study the space $\mathscr H^2_m(\triangle^{\!n}_{_P})$ and the multiplication $n$-tuple $\mathscr M_z$ acting on $\mathscr H^2_m(\triangle^{\!n}_{_P}).$ It turns out that $\mathscr M_z$ is never rationally cyclic. Although the dimension of the joint kernel of $\mathscr M^*_z-\lambda$ is constant of value $1$ for every $\lambda \in \triangle^{\!n}_{_P}$, it has jump discontinuity at the serious singularity $0$ of the boundary of $\triangle^{\!n}_{_P}$ with value equal to $\infty.$ We capitalize on the notion of joint subnormality to define a Hardy space on $\triangle^{\!n}_{_0}.$ This in turn gives an analog of the von Neumann's inequality for $\triangle^{\!n}_{_0}.$Comment: Revised version with a figure; 42 page

IN SILICO ANALYSIS AND DOCKING STUDY OF THE ACTIVE PHYTO COMPOUNDS OF MORINGA OLEIFERA AGAINST MARBURG VIRUS VP35 PROTEIN

Objective: Marburg is a transmissible disease of the Filoviridae family. It infected a million people worldwide. Hence, an attempt was made to identify natural compounds from Moringa oleifera, having multiple medicinal values in Indian Ayurveda, to prevent the disease, using molecular docking, drug likeness prediction, absorption, distribution, metabolism, and excretion (ADME) analysis, and toxicity prediction. Methods: Marburg main protein was retrieved from the protein data bank database. The ligands with poor binding and molecules that can affect docking were removed and docking is done with the PyRx tool. ADME and drug-likeness analysis were done using Swiss-ADME and absorption, distribution, metabolism, excretion, and toxicity (ADMET) lab web server. Results: Ramachandran plot analysis shows the statistical distribution of the combinations of the backbone dihedral angles ϕ and ψ of the protein. Molecular docking studies show three compounds from M. oleifera have potential binding affinity to resist the main protein VP35 by preventing proteolytic cleavage, translation, and replication of the virus. ADMET profile and drug likeness and toxicity prediction showed that all three compounds Melanin, Diclazuril, and Tifentai were safe and possess drug-like properties. Conclusion: The present study suggests that Melanin, Diclazuril, and Tifentai have significant binding affinity and they could inhibit the main protein VP35 and also helps to manage the therapeutic strategies against Marburg Virus