Divisi Biologi Molekuler dan Genetika, Generasi Biologi Indonesia Foundation

Jl. Swadaya Barat No. 4, Semampir, Cerme, Gresik, Jawa Timur

Viol Dhea Kharisma, S.Si., AMRSB

DISKUSI SANTUYY COVID-19 “Peranan Pendekatan Komputasi dalam Proses Penelitian Obat dan Vaksin“

Apa Itu SARS-CoV-2/COVID-19 ?

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from International Committee on Taxonomy of Viruses (ICTV) & Coronavirus Disease (COVID-19) from World Health Organization (WHO)

• SARS-CoV-2 belongs to the broad family of viruses known as coronaviruses

• It is a positive-sense single-stranded RNA (+ssRNA) virus

• Each SARS-CoV-2 virion is approximately 50–200 nanometres in diameter

Illustration of a SARS-CoV-2 virion

(https://phil.cdc.gov/details.aspx?pid=23312) • The WHO considers bats the most likely natural

reservoir of SARS-CoV-2

Kok Bisa Coronavirus Mengenai Manusia ?

Sumber : Epomedicine

ADAPTASI SEL INANG

VIRUS TIPE BARU

Rekombinasi Genetik Mutasi

COVID-19 vs Virus Influenza

Source Image: Horsetalk NZ

Virus Influenza Source Image: Science Friday

Virus Influenza

Struktur Virus

Image Source: (https://www.assaygenie.com/)

• Like other coronaviruses, SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane glycoprotein, and N (nucleocapsid protein)

• N protein holds the RNA genome

• S, E, and M proteins together create the viral envelope

• The spike protein is the protein responsible for allowing the virus to attach to the membrane of a host cell

• SARS-CoV-2 has sufficient affinity to the angiotensin converting enzyme 2 (ACE2) receptors of human cells to use them as a mechanism of cell entry.

Molecular Simulation of Complex SARS-CoV-2 Glycoprotein-ACE2 (these manuscript is under review by publisher)

Contoh Simulasi Komputasi

• Spike glycoprotein S1 attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.

• Binding to human ACE2

• Internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein

Bagaimana caranya agar kita dapat menentukan strategi yang tepat untuk mendesain obat maupun vaksin dari COVID-19 melalui komputasi ?

Proses Perbanyakan COVID-19

Vaksin Obat

Problematika Waktu Penelitian

Image Source: Researchgate

Mengenal Bioinformatika

Mengenal Bioinformatika

Alat Penelitian Komputasi

Database

Webserver

Software

https://www.ncbi.nlm.nih.gov/

https://pubchem.ncbi.nlm.nih.gov/ >seq COVID MFVFLLLSVPRDVVLTGRVLVYIRGFNCG

https://swissmodel.expasy.org/

https://pyrx.sourceforge.io/ https://pymol.org/2/

Contoh Data Penelitian COVID-19 >MN908947.3_NCBI MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSSSGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTESNKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSPRRARSVASQSIIAYTMSLGAENSVAYSNNSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALTGIAVEQDKNTQEVFAQVKQIYKTPPIKDFGGFNFSQILPDPSKPSKRSFIEDLLFNKVTLADAGFIKQYGDCLGDIAARDLICAQKFNGLTVLPPLLTDEMIAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRFNGIGVTQNVLYENQKLIANQFNSAIGKIQDSLSSTASALGKLQDVVNQNAQALNTLVKQLSSNFGAISSVLNDILSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLIRAAEIRASANLAATKMSECVLGQSKRVDFCGKGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDGKAHFPREGVFVSNGTHWFVTQRNFYEPQIITTDNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLIDLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT

Kode Genetik Protein Spike COVID-19

Model Struktur 3D Spike COVID-19

©Arif Nur Muhammad Ansori & Viol Dhea Kharisma

Contoh Data Penelitian COVID-19

Pemetaan Epitop Sel B Pada Spike COVID-19 Peptida Kandidat Vaksin COVID-19 Berikatan Pada

Reseptor Sel B

©Arif Nur Muhammad Ansori & Viol Dhea Kharisma

Contoh Hasil Riset Komputasi Desain Obat

Simulasi Pengikatan Senyawa Kandidat Obat Berbasis Bahan Alam Pada Protein

Fungsional HIV-1

Referensi: Kharisma, V. D., Septiadi, L., & Syafrudin, S. (2019). Prediction of Novel Bioactive Compound from Zingiber officinale as Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) of HIV-1 through Computational Study. Bioinformatics and Biomedical Research Journal, 1(2), 49-55.

Sumplemen Referensi

SARS-CoV-2

Bioinformatics

Ji, W., W. Wang W, X. Zhao, J. Zai, & X. Li. 2020. Cross-species transmission of the newly identified coronavirus 2019-nCoV. J. Med. Virol. 92(4):433-440. doi: 10.1002/jmv.25682.

Guo, Y. R., Cao, Q. D., Hong, Z. S., Tan, Y. Y., Chen, S. D., Jin, H. J., Tan, K. S., Wang, D. Y., & Yan, Y. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Military Medical Research, 7(1), 11. https://doi.org/10.1186/s40779-020-00240-0

https://www.nytimes.com/interactive/2020/03/11/science/how-coronavirus-hijacks-your-cells.html

Cao, Y., Li, L., Feng, Z. et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov 6, 11 (2020). https://doi.org/10.1038/s41421-020-0147-1

Ansori, A.N.M., & V.D. Kharisma. 2020. Characterization of Newcastle Disease Virus in Southeast Asia and East Asia: Fusion Protein Gene. EKSAKTA: Jurnal Ilmu-ilmu MIPA. 20(1): 20-28. doi: 10.20885/eksakta.vol1.iss1.art3

Adianingsih, O.R., & V.D. Kharisma. 2019 Study of B cell epitope conserved region of the Zika virus envelope glycoprotein to develop multi-strain vaccine. J. Appl. Pharm. Sci. 9(01):098–103.

Syafrudin, S., Septiadi, L., Alfaruqi, N., Wahyudi, D. and Kharisma, V. (2018) “The In Silico Analysis and Identification of Possible Inhibitor of H5N1 Virus”, Bioinformatics and Biomedical Research Journal, 1(2), pp. 33-39.