Role of natural products towards the SARS-CoV-2: A critical review.

Despite the fact that various therapeutic compounds are being investigated, there is still a scarcity of effective and reliable therapeutic regimens to treat COVID-19. Ever since the COVID-19 pandemic, a diversity of traditional herbal treatments has been investigated to cure infected people, either alone or in conjunction with mainstream pharmaceuticals, with encouraging outcomes. In this article, we look at the latest research on the usage of natural products to alleviate the severity of COVID-19. To determine the activity of the natural products, act against SARS-CoV-2 to various targets like Mpro, ACE-II, papain-like, chymotrypsin-like proteases, and some antiviral targets. The processes underlying this preventative or therapeutic action are also examined. We used PubMed, Scopus, Google Scholar, and the WHO site to perform our review. The anti-SARS-CoV-2 impacts of various herbal extracts and purified compounds may be mediated via direct prevention of viral replication or entrance. Interestingly, certain items might avert SARS-CoV-2 from infecting human cells by blocking the ACE-2 protein or the serine protease TMPRRS2. Natural products have also been stated to suppress proteins intricate in the virus life cycle, like papain-like and chymotrypsin-like proteases. To conclude, natural products can be used alone or in combination as remedies or treatments for COVID-19. In addition, their compositions may provide insight into the development of effective and reliable antiviral drugs.

Acridine as an Anti-Tumour Agent: A Critical Review.

This review summarized the current breakthroughs in the chemistry of acridines as anti-cancer agents, including new structural and biologically active acridine attributes. Acridine derivatives are a class of compounds that are being extensively researched as potential anti-cancer drugs. Acridines are well-known for their high cytotoxic activity; however, their clinical application is restricted or even excluded as a result of side effects. The photocytotoxicity of propyl acridine acts against leukaemia cell lines, with C1748 being a promising anti-tumour drug against UDP-UGT's. CK0403 is reported in breast cancer treatment and is more potent than CK0402 against estrogen receptor-negative HER2. Acridine platinum (Pt) complexes have shown specificity on the evaluated DNA sequences; 9-anilinoacridine core, which intercalates DNA, and a methyl triazene DNA-methylating moiety were also studied. Acridine thiourea gold and acridinone derivatives act against cell lines such as MDA-MB-231, SK-BR-3, and MCF-7. Benzimidazole acridine compounds demonstrated cytotoxic activity against Dual Topo and PARP-1. Quinacrine, thiazacridine, and azacridine are reported as anti-cancer agents, which have been reported in the previous decade and were addressed in this review article.

Identification of some novel oxazine substituted 9-anilinoacridines as SARS-CoV-2 inhibitors for COVID-19 by molecular docking, free energy calculation and molecular dynamics studies.

Coronavirus disease (COVID-19), a life-threatening disease, is caused by SARS-CoV-2. The targeted therapeutics of small molecules helps the scientific community to fight against SARS-CoV-2. In this article, some oxazine substituted 9-anilinoacridines (A1-A48) was designed by docking, MM-GBSA and molecular dynamics (MD) simulation studies for their COVID-19 inhibitory activity. The docking of ligands A1-A48 against SARS-CoV-2 (PDB ID: 5R82) are performed by using Glide module, in silico ADMET screening by QikProp module, binding energy using Prime MM-GB/SA module, MD simulation by Desmond module and atomic charges were derived by Jaguar module of Schrodinger suit 2019-4. Compound A38 has the highest G-score (-7.83) when compared to all the standard compounds which are proposed for COVID-19 treatment such as ritonavir (-7.48), lopinavir (-6.94), nelfinavir (-5.93), hydroxychloroquine (-5.47) and mataquine (-5.37). Compounds A13, A23, A18, A7, A48, A46, A32, A20, A1 and A47 are significantly active against SARS-CoV-2 main protease when compared with hydroxychloroquine and mataquine. The residues GLN19, THR24, THR25, THR26, LEU27, HIE41, SER46, MET49, ASN119, ASN142, HIE164, MET165, ASP187, ARG188 and GLN189 of SARS-CoV-2 main protease play a crucial role in binding with ligands. The in silico ADMET properties of the molecules are within the recommended values. The binding free energy was calculated using PRIME MM-GB/SA studies. From the ligands A38, A13, A23, A18, A7, A48 and A46 with significant Glide scores may produce significant COVID-19 activity for further development. Compound A38 was subjected to MD simulation at 100 ns to study the dynamic behaviour of protein-ligand complex.Communicated by Ramaswamy H. Sarma.