Khoa hoc Y - DUOC I DUOc hoc i DOI: 10.31276/VJST.64(12).39-47 Danh gia kha nang urc che cac di'ch phan tir virus SARS-CoV-2 ciia cac hup chat cay Xuyen tam lien bang phirung phap docking phan tu f \ Ta Thj Thu Hang1, Nguyen Bao Kim1, Nguyen Hong Nhung1, Vu Khanh Linh1, D6 Thj Hong Khanh1, Phan Van Ngoc2, Nguyen Thanh Hai1, Bui Thanh Tung1* 'T ru o n g D a i hoc Y D u g c, D a i hoc Q uoc g ia H a N o i C ong ty Co p h a n D u o c p h a m Q uang B inh N g a y n h a n b a i /7 /2 2 ; n g a y c h u y e n phan bien 2 ; n g a y n h an p h an b ie n /7 /2 2 ; n g a y ch a p n h a n d a n g /7 /2 2 T o m tat: COVID-19 la mot benh truyen nhiem lien qoan den viem duong ho hap cap virus SARS-CoV-2 gay Co1che xam nhap va lay nhiem cua no dune biet den thong qua protein S, SCL1*™,enzym chuyen doi angiotensin (ACE2) va ARN polymerase phu thuoc RNA (RdRp) Vi the, chung la cac dkb qnan trong sir ire chi lay nhiem virus SARS-CoV-2 Cay Xuyen tam lien (.Andrographis paniculata) dirge chirng minh la co kha nang uc che su nhan len cua mot so virus Nghien ciru nav danh gia tac dung ire che cac dich protein S, 3CL1” , ACE2 va RdRp cua cac hop chit cay Xuyen tam lien blng phirong phap docking phan tir Cau true 3D cua RdRp, main protease (3CL1"), protein S va ACE2 dugc lly tir Ngan hang dir lieu protein RCSB Cac hop chat dirge thu thap tir cac tai lieu ve phan hoa hoc cua cay Xuyen tam lien va cac cau true dirge lay tir cer so d r Ben PubChem Thuc hien docking phan tir banp phan mem Autodock vina Luat Lipinski dirge sir dung de danh gia kha ning d$c tinh giong thuoc cua cac hop ch at Thong so dnot dong hgc cua cac hop chit dim nang dugc danh gia qua cong c f pkCSM Dfa tren cac cong bo tririrc day ve cay Xnyen tam Ben, 22 hyp chat thu thap diroc la phan hoa hpc chinh co cay Ketqna cho thly, hop chat 3-0-beta-D-Glucopyranosyl-14,19-dideoxy andrographolide co tac dung ire che manh tren ca dich RdRp n enzym 3CLpro cua virus SARS-CoV-2 Phan tich dura tren luat Lipinski cho thly, hyp ch it 3-0-beta-D-Glucopyranosyl-14,lfdideoxyandrographolide co dac tinh giong thuoc Ngoai ra, ket qua dir doan thong sb duoc dong hoc cho thay, hop chat co kha nang hap thu d ruot rat tot va doc tinh thap Vi vay, 3-0-beta-D-Glucopyranosyl-14,19-dideoxyandrographolide la hop chat tiem nang co the tro thuoc dieu tri COVID-19 tir cay Xuyen tam lien Tit khoa: ACE2, Andrographis paniculata, docking, in silico, phan tir, protein S, RdRp, SARS-CoV-2,3CLpro Chi so nhan loai: 3.4 D£t van fle la p r o te in g a i ( S ) , p r o te in b a o b o c ( E ) , p r o te in m a n g ( M ) v a C O V I D - la m o t b e n h tr u y e n n h ie m li e n q u a n d e n v i e m d u o n g h o h a p c a p , c o n g u o n g o c tir m o t c h q b a n h a i s a n th a n h p h o V u H a n , tin h H o B a c , T r u n g Q u o c d o v ir u s S A R S - C o V - g a y [1 ] , T in h d e n n g a y / / 2 , t h l g i d i c o b a n tr ie u c a n h ie m b e n h v a g a n ,4 tr ie u c a t u v o n g v i C O V I D - [2 ] V ie t N a m tin h d e n n g a y / / 2 c o h o n ,7 tr ie u c a n h ie m , tr o n g d o d a k h o i h o n ,8 tr ie u c a v a tur v o n g h o n n g h in c a C a c tr ie u c h u n g c u a n g u d i n h ie m v ir u s S A R S - C o V - t d a p r o te in n u c le o c a p s id ( N ) [7 ] P r o te in S la m o t g ly c o p r o t e in tr im e r ic T M b a o p h u b e m a t c u a v ir u s v d i s o l u o n g ld n d u g c g l y c o s y l h o a v a li e n k e t v d i A C E c u a te b a o c h u ld p I P r o te in S c o c h u c n a n g c h in h la k e t h o p v d i th u th e v a h o p n h a t v ir u s [ , ] , - c h y o m o t r y p s i n li k e p r o te a s e ( C L pro) c o n g o i la m a in p r o t e a s e - m o t e n z y m q u a n tr o n g d o i v d i s u s a o c h e p c u a v ir u s , d a c b ie t e n z y m n a y p h a n c a t c a c p o ly p r o t e in d u g c d je h m a tir R N A c u a v ir u s d e ta o c a c p r o te in churc n a n g [1 ] pbo i thu the c h u [ 1 - ] A C E b a o gom 850 c h u o i tr in h t u H E X X H - E lien k i t A C E la m o t p r o te in m a n g lo a i I d u g c tim th a y d d a n g , c o th e k h o n g c o tr ie u c h u n g h o a c v ie m d u o n g h o h a p c a p v a s u y d a ta n g C a c tr ie u c h u n g t u o n g t u n g u d i b i n h ie m th a n , r u o t, t im v a d u g c v ir u s S A R S - C o V - d u n g la m tr u n g d u d n g h o h a p k h a c n h u s o t , d a u h o n g , h o , k h o th d , n h u c d e x a m n h ie m v a o t e b a o d a u , m e t m o i , d a u c o B e n h c o th e t ie n tr ie n n a n g d i n d i n v i e m a x it a m in , tr o n g d o c o m o t p h o i, s u y h o h a p v a t u v o n g d m o t s o it b e n h n h a n v a o tu a n v d i k e m ( Z n ) T h u th e A C E d o n g v a i tro q u a n tr o n g d 6i v o i d a u tie n k h i n h ie m b e n h b d i c o sir g ia ta n g m a n h m e c u a c a c S A R S - C o V - v i A C E g iu p v ir u s td i c a c t e b a o p h e c y t o k i n e g a y v i e m [3 ] N g o a i ra, c a c b e n h l y d i k e m n h u d a i th a o d u d n g , t a n g h u y e t a p , c a c b e n h v e tim m a c h v a h o h a p c u n g la m n a n g t h e m tin h tr a n g c u a n g u d i b e n h [4 ], V ir u s S A R S - C o V - la lo a i v ir u s c o A R N s g i d o n [5 ] , B o nang [14J loai en zv a ch e p« A R N p o ly m e r a s e p h u th u o c R N A (R d R p ) - m o t q u a n tr p n g , c o v a i tr o q u a n tr g n g tr o n g q u a trin h p h ie n m a R N A tr o n g te b a o c h u [ ] , la m o t t r o o g i d a y h u a h e n d e p h a t tr ie n th u o c S A R S - C o \ - M I bao i g e n c u a n o m a h o a a x it a m in , c o c h ie u d a i la 8 b p e n z y m v ir u s k h o n g c o c h a t t u o n g d o n g te [ ] C a c p r o te in c a u tr u e q u a n tr o n g n h a t c u a C O V I D - c h e c h o n lo c tren d ic h R d R P it ta c d o n a d i n c n c t f T ac gia lien he: Email: tungasia82@gmail.com 64(12) 12.2022 39 Khoa hoc Y - DUdc I Du'o’c hoc Evaluating inhibitory activity of bioactive compounds from A n drograph is pan icu lata against the molecular targets of the SARS-CoV-2 virus by using the molecular docking method Thi Thu Hang Ta1, Bao Kim Nguyen1, Hong Nhung Nguyen1, Khanh Linh Vu1, Thi Hong Khanh Do, Van Ngoc Phan2, Thanh Hai Nguyen1, Thanh Tung Bui1* 1U niversity o f M edicine a n d P harm acy, Vietnam N a tio n a l University, H anoi 2Q uang B inh P h a rm aceutical J o in t S to ck C om pany R e c e iv e d J u ly 2 ; a c c e p te d J u ly 2 Abstract: Covid-19 is an infectious disease associated with acute respiratory infections caused by the SARS-CoV-2 virus Its entrance and infection mechanisms have been identified as S protein, main protease (Mpro or 3CLpro), angiotensin-converting enzyme (ACE2), and RNA-dependent RNA polymerase (RdRp) As a result, they are critical targets in the prevention of SARS-CoV-2 viral infection Andrographis paniculata has been shown to be potentially effective in the treatment of several viruses This study evaluated the inhibitory effects of compounds in Andrographis paniculata against the S protein, 3CLpro, ACE2, and RdRp targets by molecular docking method The 3D structure of the SARS-CoV-2 RdRp, 3CLpro, S protein and ACE2 were obtained from the RCSB Protein Data Bank Compounds were collected from the publication of Andrographis paniculata and these structures were obtained from the PubChem database Molecular docking was done by AutoDock Vina software Lipinski rule of five is used to compare compounds with drug-like and non-drug-like properties Pharmacokinetic parameters of potential compounds were evaluated using the pkCSM tool Based on previous publications of Andrographis paniculata, 22 main compounds were collected The results showed that the compound 3-0-beta-D-Glucopyranosyl-14,19dkfeoxyandrographolide had a strong inhibitory effect on both the RdRp and 3CLpro targets of SARS-CoV-2 virus Analysis of Lipinski 5’s rule exhibited that 3-O-beta-D-Glucopyranosyl14.19-dideoxyandrographolide has drug-likeness properties In addition, the results of predicting pharmacokinetic parameters ■ d ieated that this compound had good intestinal absorption and law toxicity The compound 3-0-beta-D-Glucopyranosyl-14,19tfdeaxyaadrographolide is a potential compound to become the f e n p e s t k drug Covid-19 from Andrographis paniculata i d s e f e ACE2 Andrographis paniculata, docking, in silico, n g o a i te b a o d ic h , d o d o c o t h e d u g c p h a t tr ie n d e c a i t h ie n h ie u q u a v a it g a y c a c ta c d u n g k h o n g m o n g m u o n D a y c h in h la li e u p h a p d ie u trj COVID-19 a n t o a n v a h ie u q u a h o n s o v d i trc c h e c a c d ic h p h a n t i i k h a c [ ] C a y X u y e n ta m lie n d a d ir g e s u d u n g d e d ie u tri n c a n , t ie u d u d n g , k ie t l y , s o t v a s o t ret [ ] , P h a n tr e n m a t d a t c u a c a y n a y c o c h u a d it e r p e n o id s , d it e r p e n e g l y c o s i d e , la c t o n , f l a v o n o id v a f l a v o n o id g l y c o s i d e X u y e n ta m lie n d a d u g c b a o c a o la c o m o t lo a t c a c ta c d u n g d ir g e ly n h u c h o n g u n g th u [ ] , H I V [ ] , a n tid ia r r h e a l [ ] , a n tih e p a tit is [ ] , h a d u d n g h u y e t [ 2 ] , k h a n g k h u a n , c h o n g s o t ret [ , ] , c h o n g v i e m , c h o n g o x y h o a [ ] , t im m a c h [ , ] , b a o v e g a n [ ] , k ic h th ic h m ie n d je h [ , ] T r o n g m o t n g h ie n c u u c h o th a y , m o t h o p c h a t tr o n g c a y X u y e n ta m li e n la a n d r o g r a p h o lid e d u g c d a n h g ia in vitro v d i k h a n a n g la m g ia m q u a trin h n h a n le n c u a v ir u s S A R S c o r o n a v ir u s v d i g i a tri E C S0= , p g /m l [ ] , D o d o , c a y X u y e n ta m li e n d ir g e lu a c h o n v d i m u c d ic h s a n g lo c c a c h o p c h a t c o tr o n g c a y v a d a n h g i a h ie u q u a c u n g n h u t ie m n a n g trd th a n h th u o c tr o n g d ie u tri S A R - C o V - D o c k i n g p h a n tir la m o t k y th u a t m o h in h h o a v d i m u c d ic h d u d o a n v i tri v a c a u h in h m a p h o i t u ( lig a n d ) c o t h e li e n k e t v d i p h a n t u p r o te in (ta r g e t) P h o i tur d u g c c h o d ic h c h u y e n tr o n g k h o n g g ia n b a o q u a n h p h a n t u p r o te in d e tim v i tri c o k h a n a n g g a n k e t b e n v u n g n h a t s u d u n g c a c h a m d a n h g i a v a p h u ern g p h a p t im k ie m c u e tri to a n c u e k h a c n h a u T u d o c o th e t im d u g c n h u n g h o p c h a t c o ta c d u n g u c c h e p r o te in [ ] , P h u o n g p h a p d o c k in g p h a n tir n a y c o iru d ie m t i e t k ie m th d i g ia n v a c h i p h i tr o n g v i e c s a n g l o c c a c h o p c h a t s o v d i c a c p h u o n g p h a p t h u c n g h ie m [ 3 ] , M u c t i e u c u a n g h ie n c u u n a y l a s a n g l o c c a c h o p c h a t c o ta c d u n g u c c h e c a c d ic h p h a n tur p r o t e in S , C L pro, A C E v a R d R p c u a c a c h g p c h a t tr o n g c a y X u y e n ta m li e n b a n g p h u o n g p h a p d o c k in g p h a n t u n h a m tim k ie m h o p c h a t c o th e p h a t tr ie n th a n h th u o c d e d ie u tri S A R S - C o V - Nguyen li$u va phirofng phap nghien ciiti Mo hinh docking C h u d n h i c d u tru e p ro te in : C a u tr u e 3D cua en zym S A R S - C o V - R d R p ( P D B ID : M ) , C L pro ( P D B ID : W ) , p r o te in S ( P D B ID : 6V Y B ) v a A C E ( P D B ID : R L ) d u g c tr u y x u a t t u N g a n h a n g d u li e u p r o te in R C S B ( w w w r c s b o r g ) P r o te in S c u a S A R S - C o V - v d i I D 6V Y B b a o g o m c h u o i: A , B , C v a c h u o i A d u g c ta c h d e s u d u n g c h o m o h in h d o c k in g [ ] , H a i p h o i t u d o n g k e t tin h X 7 v a X X c u a C L pro (I D : W ) v a A C E (I D : R L ) d u g c s u d u n g d e d a n h g ia v a t o i u u h o a m o h in h d o c k in g V u n g h o a t d o n g c u a p r o te in d u g c x a c d in h b a n g p h a n m e m M O E v a D i s c o v e r y S t u d io V is u a l iz e r D e c h u a n b i c h o q u a tr in h d o c k in g , ta t c a c a c p h a n t u n u d e v a d o n g t in h t h e d a d u g c lo a i b o k h o i p h a n t u p r o t e in b a n g p h a n m e m D i s c o v e r y S t u d io V is u a l iz e r C a c p h a n t u h y d r o g e n d u g c t h e m v a o b a n g p h a n m e m A u t o d o c k V in a tr u d e k h i ta i la p v u n g h o a t d o n g c u a p r o te in s u d u n g p h a n m e m M G L A u t o d o c k t o o l s T r u n g ta m h o a t d o n g c u a R d R p , C L pro, p r o te in S v a A C E d u g c x a c d jn h d b a n g 40 Khoa hoc Y - DUOc I DUOc hoc Bang Trung tarn hoat dong cua protein quan D ir d o a n c a c th o n g so du q 'c d o n g h o c Protein Rich thiroc hop liroi (A) (x,y,z) Rdrp 30x30x30 (121, 120 125) h a p th u , p h a n b o , c h u y e n h o a , th a i trir v a d o c tin h ( A D M E T ) 3CLp'» 20x20x20 (-20.313 18.742.-28341 > c u a c a c h g p c h a t t ie m n a n g d u g c d a n h g i a q u a c o n g c u p k C S M Spike protein 12x10x13 (197.044 222.794.205.696- ( h t t p : //b io s ig u n im e lb e d u a u /p k c s m /p r e d ic t io n ) [ ] ACE2 12x10x13 (40,003 6,069 28338 > K6t qua C h u a n b i c a n tru e p h o i tit: K et qua d u d o a n c a c th o n g so v e d u g c d o n g h g c b a o g o m D u a tren c a c c o n g b o tn r o c d i y D a n h g ia m o h in h d o c k in g th u th a p d u g c 2 h o p c h a t c o k h a n a n g ire c h e S A R S - C O Y - tir c a y X u y e n ta m lie n [ , ] , C a u tru e D c u a n h u n g h o p T r u o c k h i s a n g lo c c a c h g p c h a t, m o h in h d o c k in g c a n d u g c c h a t n a y d u g c la y tir c o s o d u lie u P u b C h e m o d in h c a n c s d f d a n h g ia tin h c h in h x a c c u a n o K e t q u a sa u k h i d o c k in g la i sa u d o c h u y e n th a n h d in h d a n g p d b b a n g p h a n m e m C h im e r a p h o i t u d o n g tin h th e th u d u g c g ia trj R M S D la n l u g t la , [ , ] T ie p t h e o , c a c p h o i t u d u g c to i u u h o a b a n g p h ir m e m v a ,8 A v o g a d r o sir d u n g p h u o n g p h a p G r a d ie n t lie n h g p ( C o m g a t e n h o h o n 1,5 G r a d ie n ts ) ro i c h u y e n th a n h d in h d a n g p d b q t b a n g p h a n m e m la d a n g tin c a y A u to d o c k T o o l [3 , ], (A) T h u c h ien d o c k in g p h a n tir: A (h in h 1) H a i g ia tri n a y t h o a m a n d ie u k ie n R M S D A churng to k e t q u a d o c k in g p h a n t u v a o m u c tie u (B) C a c p h o i tir d u g c d o c k v a o tr u n g ta m h o a t d o n g c u a p r o te in b a n g p h a n m e m A u t o d o c k v in a S ir d u n g p h a n m e m D is c o v e r y S t u d io Y is u a liz e r g iu p q u a n sa t c a c lie n k e t g iu a p r o te in v a c a c h g p c h a t s a n g lo c d u g c D a n h g ia k e t q u a d o c kin g : D e d a n h g ia k e t q u a q u a trin h d o c k in g , p h o i tir tir d o n g tin h th e d a d u g c d o c k in g la i v a o v j tri h o a t d o n g c u a m u c tie u Q u a tr in h d u g c th u c h ie n th a n h c o n g n e u g i a tri d o le c h b in h p h u o n g tr u n g b in h g o c ( R M S D ) n h o h o n h o a c b a n g ,5 A D o i v b i c a c c h a t c a n d o c k in g , k h a n a n g Hinh Ket qua re-dock phoi tCr dong ket tinh cua phu>c hgp 6W63 (A) va 1R4L (B) g a n k e t c u a c h u n g d u g c d a n h g i a th o n g q u a t u o n g ta c \ d i c a c S ir t u o n g ta c g i u a p h o i t u d o n g k e t tin h v d i C L pro v a A C E a x it a m in tr o n g tr u n g ta m h o a t d o n g c u a p r o te in v a n a n g l u g n g t u o n g ta c d u g c tin h b o i h a m tin h d ie m ( s c o r in g f u n c t io n ) c u a d u g c th e h ie n a h in h A u t o d o c k v in a M o liin li d o c k in g c u a c a c h o p c h a t v d i d ic h p r o te in D a n h g ia q u y ta c tie u c h i c u a L ip in s k i S a u k h i c h u a n b i p h o i tu , tie n h a n h d o c k in g 2 h g p ch a t Q u y ta c t ie u c h i c u a L ip in s k i d u g c sir d u n g d e d a n h g ia th ie n n h ie n tu c a y X u y e n ta m lie n d e s a n g lp c h o a t d o n g u c d a c tin h g i o n g th u o c c u a c a c h g p c h a t [4 ] t h o n g q u a c o n g c h e c a c p r o te in d ic h c u a S A R S -C O V -2 c u a c h u n g K e t q u a cu d u g c t h e h ie n a b a n g o n li n e ( h t t p : // w w w s c f b io - ii t d r e s i n /s o f t w a r e / d r u g d e s i g n / lip in s k i.j s p ) [ ] THR A:371 In te c tio n s Interaction* " ] van der Waats 2] Convention^ Hydrogen Bond | PPH ) Carbon Hy^ogen Bond ■I PPH Pl-SUfur Amde-bi Stacked Salt Bridge Attractive Charge T-shaped [ " | Pi-Akyt unfavorabte Donor -Oonor ||g g | ■■ Conventional Hydrogen Bond ■ ■ ■ Pi-Cation ■ H Pi-Anion Hinh Bieu dien 2D tiFcyng tac cua phoi tu5dong ket tinh X77 vo»i 3CLpro (A) va XX5 vo»i ACE2 (B) TAP CHl IC H O A H O C C ONG NG H E am 64(12) 12.2022 41 Khoa hoc Y - Dupe I D u o c hoc Bang Ket qua docking cua 22 hop chat, cac phoi tip dong ket tinh (X77, XX5) va cac chit chtmg dirong (Artemisinin, remdesivir) STT Hop chat RdRp (6m71) ACE2 (1R4L) l A ndrographolide -6,8 -4,3 3C L'" (kealmol) (6W63) -7 -5,3 Neoandrographolide -7,9 -3,8 -7 ,8 -5,9 14-D eoxyandrographolide -6,2 -4,7 -7 J -5,3 Andrographiside -7,9 -4,0 -7,8 -6,1 Isoandrographolide -6,8 -4,2 -7 ,9 -5,8 Andrographic axit -7,1 -3,8 -7 ,0 -5,5 Andrograpanin -6,1 -4,6 -7,4 -5,2 3-O -beta-D -G lucopyranosyl-l ,1 dideoxyandrographolide -8,7 -4,6 -8,1 -6,1 A ndrographolactone -6,2 -4,5 -7,5 -5,5 10 12-H ydroxyandrographolide -6,7 -4,8 -7 ,4 -5,0 11 A ndropanolide -6,2 -4,4 -7 ,0 -5,6 12 A ndrographatoside -7,3 ^*,1 -7 ,4 -5,9 13 Bisandrographolide -8,6 -3 ,9 -8,2 -6,6 14 Dehydroandrographolide -6,4 -4,3 -6,9 -5,6 14 14 -d e o x y -11,12-didehydroandrographolide -6,3 -4,4 -7,4 -5,5 16 14 -d e o x y -14,15-dehydroandrographolide -6,5 -4 ,4 -7,6 -5,5 17 ,1 9-isopropylideneandrographolide -7 ,6 -4,7 -8,1 -5,9 18 5-hydroxy-7,8-diraethoxyflavone -6,5 -4,2 -7,0 -5,3 19 5-hydroxy-7', 8', 2', 5'-tetram ethoxyflavone -6,4 -4,2 -7,4 -5,4 20 5-hydroxy-7', 8', 2', 3'-tetram ethoxyflavone -6 ,4 -4,0 -6,8 -5,6 21 5-hydroxy-7', 8', 2'-trim ethoxyflavone -7 ,6 -3,7 -7,9 -5,9 22 7-O -m ethylw ogonin -6,5 -4,2 -7,0 -5,3 23 R em desivir ( R l) -7,5 24 A rtem isinin (R 2) 25 X 7 (R 3) 26 X X (R 4) Protein S (6VYB) -7,3 -8,6 -7,5 R e m d e s iv ir la th u o c d a u tie n d u g c c u e Q u a n ly t h u c p h a m v a n a y tie n h a n h s o sa n h n a n g l u g n g g a n k e t c u a c a c h g p c h a t tie m D u g c p h a m H o a K y ( F D A ) c h a p th u a n d e d ie u tri C O V I D - n a n g v o i r e m e s d e v ir v a a r t e m is in in ( c h a t c h u n g d u o n g d e d a n h n h d b a n g c h u n g d a n g k e v e h ie u q u a v a ti'nh an t o a n c u a n o g ia k h a n a n g u c c h e e n z y m R d R p v a p r o te in S c u a c h u n g ) [ 4 ] , R e m d e s i v ir la m o t c h a t u c c h e R d R p , d o d o c o t h e u c c h e V e k h a n a n g u c c h e C L pro v a A C E c u a c a c h g p c h a t th u sir n h a n le n c u a c o r o n a v ir u s tr o n g c a c t e b a o b ie u m o d u d n g h o d u g c , n a n g l u g n g lie n k e t v o i h a i p h o i t u d o n g k e t tin h sa u k h i h a p [ ] A r t e m is in in c u n g d a d u g c c h u n g m in h k h a n a n g h o a t d o c k in g la i s e d u g c s u d u n g d e s o s a n h K e t q u a h in h c h o th a y d o n g n h u m o t c h a t u c c h e p r o te in S [ ] D o d o , n g h ie n c u u lie n k e t c u a R d R p v o i r e m d e s iv ir , p r o te in S v o i a r te m is in in Interactions van der Waals S - - - : = ; e - 2D Conventional Hydrogen Bond tuomg tac cua RdRp voi remdesivir (A), protein S voi artemisinin (B) 6+ 12) 12.2022 42 I 1 Pi-Alkyl Khoa hoc Y - DUOc I DUOc hoc T ir b a n g ta th a y , h a p c h a t c o n a n g l u g n g lie n k e t th a p D o i v a i d ic h p h a n t u p r o te in S v a A C E , p h a n t u h a n r e m d e s iv ir ( - ,5 k c a l/ m o l ) , b a o g o m n e o a n d r o g r a p h o lid e c o n a n g l u g n g lie n k e t c a o h a n s o v d i (- ,9 a r t e m is in in k c a l/ m o l ) , a n d r o g r a p h is id e ( - ,9 k c a l/ m o l ) , va phoi tu dong chat ch u n g d u a n g k e t t in h XX5 -O -b e ta -D - -0 - b e ta -D -G lu c o p y r a n o s y l-1 ,1 -d id e o x y a n d r o g r a p h o lid e g l u c o p y r a n o s y l - ,1 - d i d e o x y a n d r o g r a p h o l i d e ( - ,7 k c a l/ m o l ) , b is a n d r o g r a p h o lid e ( - 8,6 k c a l m o l l H em n u a , l u g n g li e n k e t th a p n h a t v a i R d R p ( - ,7 k c a l / m o l ) , d u g c d o c k h a p c h a t n a y lie n k e t v a i C L pr0 v a i n a n g lu g n g k h a th a p v a o v u n g h o a t d o n g c u a e n z y m n a y v a i v i tri t u a n g t u n h u c u th e la n e o a n d r o g r a p h o lid e ( - ,8 k c a l m o l ) a n d r o g r a p h is id e ( - ,8 k c a l/ m o l ) , -0 -b e ta -D -G lu c o p y r a n o s y l-1 i9 - d id e o x y a n d r o g r a p h o lid e ( - 8,1 k c a l m o l l, b is a n d r o g r a p b o lid e ( - ,2 k c a l/ m o l ) T u a n g ta c p h o i tir - v a i a x it a m in R d R p ( h in h ) v a C L pro (h in h ) c h o th a y c h u y e u la t u a n g ta c q u a lie n k e t h ydro v a n co nang r e m d e s iv ir H g p c h a t n a y li e n k e t v a i p r o t e in d ic h q u a c a c li e n k e t h y d r o v a i A S P , G L U 1 , T R P 0 , S E R v a L Y S B is a n d r o g r a p h o l id e c u n g c h o th a y n h u n g tu o n g ta c t u a n g t u v a i R d R p , q u a c a c a x it a m in A S P , A R G 5 , C Y S 2 v a A S P N e o a n d r o g r a p h o lid e v a a n d r o g r a p h is id e C a c a x it a m in c u a p r o te in v ir u s n a y v a i h a p c u n g c o n a n g l u g n g li e n k e t k h a th a p v a i e n z y m v ir u s n a y c h a t t ie m n a n g d ir g e th e h ie n a b a n g q u a n h u n g a m i n o a x it t u a n g t u , li e n k e t h y d r o v a i A S P , Bang Bon hop chat tiem nang lien ket von cac axit amin cua RdRp va 3CLpro vung hoat dong tuxmg img A S P v a A R G 5 S o sa n h t u a n g ta c c u a h g p c h a t n a y v a C L pro v a i p h o i tir d o n g k e t tin h X 7 c o t h e th a y , lie n k e t STT Ten Neoandrographolide p h o i t u - a x it a m in c u a h a u h e t c a c h g p c h a t c u n g t u a n g t u Lien ket vdi n il amin Lie* kfl vdi n k a n cua RdRp cu X L - n h a u D o la n h u n g a x it a m in q u a n tr o n g n h u A S N , H I S ASP618, SER795 H1S41 MET-W GLM89 va M E T 49 ARG553 THR25.THR190 K e t q u a q u y la c tie u c h i c u a L ip in s k i ASP761, LYS798, Andrographiside GLU811, CYS813, THR25.CYS44.HIS4I SER8I4, TRP800 3-0-beta-D-Glucopyranosyl14,19-dideoxyandrographolide Bisandrographolide u n g it n h a t tr o n g c a c t i e u c h i c u a lu a t L ip in s k i: ( ) K h o i ASP761, GLU811, HIS41, MET49, HIS163, l u g n g p h a n t u < 0 D a : ( C o t in h u a d i u c a o I L o g P n h o h a n TRP800, SER795, LEU141, PHE140, ASN142, ) ; ( ) K h o n g c o n h ie u h a n n h o m c h o LYS798 THR190 ASP623, ARG553, C a c h o p c h a t d u g c g o i la " g i o n g th u o c " k h i c h u n g d a p CYS622, ASPI64, PHE793 LEU141, ASN142, GLY143 le n k e : h > d r a g K h o n g c o n h ie u h a n n h o m n h a n li e n k e t h y d r o g e n : k h u c x a m o l p h a i n a m tr o n g k h o a n g q u y ta c t i e u c h i c u a L ip in s k i c u a Do 40-130 K^t qua dap in g hop chit tren dugc trinh bay a b an g 1(C) '_ / i ’ * ' \ Hinh Bieu d iin sir tirorng tac cua neoandrographolide (A), andrographiside (B), 3-O-beta-D-Glucoc dideoxyandrographolide (C), bisandrographolide (D) veri RdRp bieu d iin 2D (phai) va 3D (trai) IAr (.HI 64(12) 12.2022 43 ‘ 5- Khoa hoc Y - Dtfcic I Duoc hoc Hinh Bieu dien su tu’O’ng tac cua neoandrographolide (A), andrographiside (B), 3-0-beta-D-glucopyranosyl-14,19dideoxyandrographolide (C), bisandrographolide (D) v