Seasonal variation of the composition of essential oils from <i>Piper cernuum</i> Vell and <i>Piper rivinoides</i> Kunth, ADMET study, DFT calculations, molecular docking and dynamics studies of major components as potent inhibitors of the heterodimer methyltransferase complex NSP16-NSP10 SARS COV-2 protein

Coronavirus disease (COVID-19) has the virus that causes the SARS-CoV-2 severe acute respiratory syndrome, which has reached a pandemic proportion, with thousands of deaths worldwide already registered. It has no standardized effective clinical treatment, arousing the urgent need for the discovery of bioactive compounds for the treatment of symptoms of COVID-19. In this context, the present study aimed to evaluate the influence of seasonality on the yield and chemical composition of the essential oils of <i>Piper cernuum</i> and <i>Piper rivinoides</i> as well as to evaluate the anti-SARS-CoV-2 potential of the major components of each oil by molecular docking and quantum chemical calculation (Density Functional Theory method), being possible indicate that the winter and autumn periods, the seasons of the year where it is possible to obtain the highest percentage of <i>Piper cernuum</i> and <i>Piper rivinoides</i> oils, respectively. Regarding the anti-SARS-Cov-2 potential, the present work showed that the dihydroagarofuran present in <i>Piper cernuum</i>, presented a strong interaction with amino acid residues from Mpro, presenting a potential similar to Remdesivir, a drug for clinical use. Regarding methyltransferase, dihydroagarofuran (<i>Piper cernuum</i>) and myristicin (<i>Piper rivinoids</i>) showed better affinity, with important interactions at the active site of the inhibitor Sinefugin, suggesting a potential inhibitory effect of the heterodimer methyltransferase complex NSP16-NSP10 SARS Cov-2. Molecular docking and molecular dynamics studies represent an initial step, being indicative for future <i>in vitro</i> studies of dihydroagarofuran and myristicin, as possible pharmacological tools for COVID-19. Communicated by Ramaswamy H. Sarma Autumn and winter are the most suitable seasons of the year to extract the oils of <i>Piper rivinoides</i> and <i>Piper cernuum</i> respectively. <i>in silico</i> evaluation of majoritary compounds of essential oils against the anti-SARS-Cov-2 potential by Molecular docking. The electronic properties were computed using the Density Functional Theory method to understand the interaction of the molecules and the amino acids. Dihydroagarofuran (<i>Piper cernuum</i>) and myristicin (<i>Piper rivinoids</i>) suggesting a potential inhibitory effect of the heterodimer methyltransferase complex NSP16-NSP10 SARS Cov-2. Dihydroagarofuran present in <i>Piper cernuum</i> suggesting a potential inhibitory effect of the Mpro.