The effect of various compounds on the COVID mechanisms, from chemical to molecular aspects.

The novel coronavirus that caused COVID-19 pandemic is SARS-CoV-2. Although various vaccines are currently being used to prevent the disease's severe consequences, there is still a need for medications for those who become infected. The SARS-CoV-2 has a variety of proteins that have been studied extensively since the virus's advent. In this review article, we looked at chemical to molecular aspects of the various structures studied that have pharmaceutical activity and attempted to find a link between drug activity and compound structure. For example, designing of the compounds which bind to the allosteric site and modify hydrogen bonds or the salt bridges can disrupt SARS-CoV2 RBD-ACE2 complex. It seems that quaternary ammonium moiety and quinolin-1-ium structure could act as a negative allosteric modulator to reduce the tendency between spike-ACE2. Pharmaceutical structures with amino heads and hydrophobic tails can block envelope protein to prevent making mature SARS-CoV-2. Also, structures based on naphthalene pharmacophores or isosteres can form a strong bond with the PLpro and form a π-π and the Mpro's active site can be occupied by octapeptide compounds or linear compounds with a similar fitting ability to octapeptide compounds. And for protein RdRp, it is critical to consider pH and pKa so that pKa regulation of compounds to comply with patients is very effective, thus, the presence of tetrazole, phenylpyrazole groups, and analogs of pyrophosphate in the designed drugs increase the likelihood of the RdRp active site inhibition. Finally, it can be deduced that designing hybrid drug molecules along with considering the aforementioned characteristics would be a suitable approach for developing medicines in order to accurate targeting and complete inhibition this virus.

The Novel Drug Discovery to Combat COVID-19 by Repressing Important Virus Proteins Involved in Pathogenesis Using Medicinal Herbal Compounds.

BACKGROUND: The cause of COVID-19 global pandemic is SARS-CoV-2. Given the outbreak of this disease, it is so important to find a treatment. One strategy to cope with COVID-19 is to use the active ingredients of medicinal plants. In this study, the effect of active substances was surveyed in inhibiting four important druggable targets, including S protein, 3CLpro, RdRp, and N protein. RdRp controls the replication of SARS-CoV-2 and is crucial for its life cycle. 3CLpro is the main protease of the virus and could be another therapeutic target. Moreover, N protein and S protein are responsible for SARS-CoV-2 assembly and attaching, respectively. METHODS: The 3D structures of herbal active ingredients were prepared and docked with the mentioned SARS-CoV-2 proteins to obtain their affinity. Then, available antiviral drugs introduced in other investigations were docked using similar tools and compared with the results of this study. Finally, other properties of natural compounds were uncovered for drug designing. RESULTS: The outcomes of the study revealed that Linarin, Amentoflavone, (-)-Catechin Gallate and Hypericin from Chrysanthemum morifolium, Hypericum perforatum, Humulus lupulus, and Hibiscus sabdariffa had the highest affinity for these basic proteins and in some cases, their affinity was much higher than antiviral medicines. CONCLUSION: In addition to having high affinity, these herb active ingredients have antioxidant, vasoprotective, anticarcinogenic, and antiviral properties. Therefore, they can be used as extremely safe therapeutic compounds in drug design studies to control COVID-19.

Manipulated bio antimicrobial peptides from probiotic bacteria as proposed drugs for COVID-19 disease.

Coronavirus disease 19 (COVID-19) is the latest pandemic resulted from the coronavirus family. Due to the high prevalence of this disease, its high mortality rate, and the lack of effective treatment, the need for affordable and accessible drugs is one of the main challenges in this regard. It has been proved that RdRp, 3CL, Spike, and Nucleocapsid are the most important viral proteins playing vital roles in the processes of proliferation and infection. Therefore, we started studying a wide range of bio-peptides and then conducted molecular docking analyses to investigate their binding affinity for the inhibition of these proteins. After obtaining the best bio-peptides with the highest affinity scores, they were examined for further study and then manipulated to eliminate their side effects. Additionally, the molecular dynamic simulation was performed to validate the structure and interaction stability. The results of this study reveal that glycocin F from Lactococcus lactis and lactococcine G from Lactobacillus plantarum had the high affinities to bind to the viral proteins, and the manipulation of their sequence also led to the side effects' elimination. In addition, in some cases, their affinities to attach the SARS-CoV-2 proteins have increased. It seems that these two drugs which were discovered and designed, are optimal for treating the COVID-19 infection. However, experimental and pre-clinical studies are necessary to assay their therapeutic effects.

Predicted therapeutic targets for COVID-19 disease by inhibiting SARS-CoV-2 and its related receptors.

The SARS-CoV-2 causes severe pulmonary infectious disease with an exponential spread-ability. In the present research, we have tried to look into the molecular cause of disease, dealing with the development and spread of the coronavirus disease 2019 (COVID-19). Therefore, different approaches have investigated against disease development and infection in this research; First, We identified hsa-miR-1307-3p out of 1872 pooled microRNAs, as the best miRNA, with the highest affinity to SARS-CoV-2 genome and its related cell signaling pathways. Second, the findings presented that this miRNA had a considerable role in PI3K/Act, endocytosis, and type 2 diabetes, moreover, it may play a critical role in the prevention of GRP78 production and the virus entering, proliferation and development. Third, nearly 1033 medicinal herbal compounds were collected and docked with ACE2, TMPRSS2, GRP78, and AT1R receptors, which were the most noticeable receptors in causing the COVID-19. Among them, there were three common compounds including berbamine, hypericin, and hesperidin, which were more effective and appropriate to prevent the COVID-19 infection. Also, it was revealed some of these chemical compounds which had a greater affinity for AT1R receptor inhibitors can be suitable therapeutic targets for inhibiting AT1R and preventing the adverse side effects of this receptor. According to the result, clinical assessment of these three herbal compounds and hsa-miR-1307-3p may have significant outcomes for the prevention, control, and treatment of COVID-19 infection.