”In silico investigation of potential inhibitors to main protease and spike protein of SARS-CoV-2 in propolis”
Azza Hanif Harisna, Rizky Nurdiansyah, Putri Hawa Syaifie, Dwi Wahyu Nugroho, Kurniawan Eko Saputro, Firdayani, Chandra Dwi Prakoso, Nurul Taufiqu Rochman, Nurwenda Novan Maulana, Alfian Novianto, Etik Mardliyati.
Docking analysis of propolis’s natural compound was successfully perform against SARS-Co V-2 main protease (Mpro) and spike protein subunit 2 (S2). Initially, the propolis protein was screened using chromatography analysis and successfully identified 22 compounds in the propolis. Four compounds were further investigated, i.e. neoblavaisoflavone, metthylophiopogonone A, 3′-Methoxydaidzin, and genistin. The binding affinity of 3′-Methoxydaizin was -7.7 kcal/mol, which is similar to nelfinavir (control), while the other were -7.6 kcal/mol. However, we found the key residue of Glue A:166 in the methylophiopogonone A and genistin, even though the predicted binding energy slightly higher than nelfinavir. In contrast, the predicted binding affinity of neo-blavaisoflavone, methylophogonone A, 3′-Methoxydaidzin, and genistin againts S2 were -8.1, -8.2, -8.3, and -8.3 kcal/mol, respectively, witch is far below of the control (pravastatin, conventional hydrogen bonding, the π bonding influenced the binding affinity against S2. The result reveal that this is the firast report about methylophiopogonone A,3′-Methoxydaidzin, and genistin as candidates for anti-viral agents. Those compounds can then be further explored and used as parent backbone molecule to develop a new supplementation for preventing SARS-CoV-2 infection during COVID-19 outbreaks.
Earlier this year, a novel coronavirus (SARS-CoV 2) triggered a coronavirus disease 19 (COVID-19) outbreak in Wuhan, China, and then spreading globally. The outbreak was announced as a Public Health Emergency of International Concern in January 2020 by World Health Organization (WHO). As of May 12, 2020, there are more than 4,324,739 confirmed cases of COVID-19, and at least 297,197 death reported, which indicated a severe public health threat. Unlike MERS-Cov but similar to SARS-CoV, SARS-CoV 2 can cause human to human transmission, and its intermediate host leading to the current human infection is still under investigation.
Any concrete solution in prevention, treatment, and post-infection are still lacking. So far, several drugs have been studied as COVID-19 treatments, such as nevilnafir, choroquine, hydrochloroquine and remdesivir. Several researchers identified potential anti-viral agents to prevent SARS-CoV-2 infection. Several FDA-approved drugs were evaluated as potential anti-viral agents. They can bind to SARS-CoV-2 RdRp and blocked its active site. Remdesivir and chloroquine also have an inhibitor activity to SARS-CoV-2 infection. Althought these drug candidates have been massively studied, its currently undergoing the clinical evaluation phase and caution must be taken to avoid any negative effects. Unfortunately, there is no apparent certainty which drug is the most effective in curing the SARS-Cov-2 infection.
It has been computationally determined that the SARS-CoV-2 has a similar mechanism and receptor to SARS, angiontensin-converting enzyme 2 (ACE2). SARS-CoV-2 uses its spike glycoprotein, which has similarities with the SARA-CoV spike protein structurally, to mediate membrane fusion. The conversion is 73% with most of the variability being in the protein’s host cell interaction region. SARS-CoV-2 spike protein is a class I viral fusion protein, which required a protease cleavage to activate the membrane fusion. It has two subunit monomers, S1 for mediating attachment and S2 for membrane fusion, with a similar length of around 180 kda. Any of them has been of the main target neutralization antibody.
“Kesimpulan dari Paper penelitian dari propolis adalah propolis mempunyai 22 senyawa baik, dan ada 4 senyawa yang diteliti yang mampu menghambat inveksi virus dan menghambat perkembangannya virus covid-19 dalam tubuh”.
Penelitian ini adalah skrining senyawaan propolis tahap awal yang menghasilkan penemuan adanya potensi senyawaan propolis sebagai anti virus covid 19 dan perlu dilakukan uji lanjutan seperti uji klinis.
Positifnya kita wajib mempunyai sebuah penelitian dan obat yang sangat baik untuk dapat menolong seluruh umat manusia untuk bahaya virus SARS-CoV-2.
Immune manusia itu sendiri yang dapat melawan segala virus berbahaya. Jangan sampai immune kita lemah karena sesuatu apapun.
Nano Center Indonesia dan team research nya selalu mengumandangkan bahwasannya banyak manfaat tentang Nano teknologi tersebut.
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