key: cord-291747-3du4jluy authors: Habashy, Noha H.; Abu-Serie, Marwa M. title: The potential antiviral effect of major royal jelly protein2 and its isoform X1 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Insight on their sialidase activity and molecular docking date: 2020-11-11 journal: J Funct Foods DOI: 10.1016/j.jff.2020.104282 sha: doc_id: 291747 cord_uid: 3du4jluy Severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 is a newly emerging type of CoV. We evaluated the predicted anti-SARS-CoV-2 effect of major royal jelly protein (MRJP)2 and MRJP2 isoform X1, which recently showed high efficacy against other enveloped RNA-viruses (HCV and HIV). Some in-silico analyses have been performed to predict the impact of these proteins on viral entry, replication, and complications. These proteins have shown a high potency in sialic acid hydrolysis from the lung cells (WI-38) surface. Docking analysis showed that these proteins have a high binding affinity to viral receptor-binding sites in the receptor-binding domain, causing attachment prevention. Moreover, MRJPs can exert an inhibitory influence, via different mechanisms, for SARS-CoV-2 non-structural proteins (main and papain proteases, RNA replicase, RNA-dependent RNA polymerase, and methyltransferase). Also, they can bind to hemoglobin-binding sites on viral-nsps and prevent their hemoglobin attack. Thus, MRJP2 and MRJP2 X1 can be a promising therapy for SARS-CoV-2 infection. Since the end of 2019 to the present, severe acute respiratory syndrome 47 coronavirus 2 (SARS-CoV-2) has caused widespread infection and is considered 48 a threat to public health security. CoVs (7 species) have a positive-sense single-49 strand RNA genome with an envelope protein containing a spike protein. The 50 latter protein forms a sun-like morphology that gives this virus its Latin name- Purification of MRJP2 and its isoform X1 125 The RJ was obtained from the local market in Egypt and used instantly The results in Fig. S5 show that nsp5, nsp9, and nsp16-nsp10 could 361 interact individually with both oxy-hemoglobin chains (Fig. S5 I-III) . Concerning the deoxyhemoglobin (Fig. S5 IV-VI) , the nsps could interact with 363 one (nsp9), two (nsp16-nsp10), or three (nsp5) chains. 365 The active site residues in the studied enzymes (nsp3, nsp5, nsp9, (Table 1) . The sites of these viral enzymes in addition to nsp16 (Table 1 , Fig. 2, 3, S3, S4 ). Therefore, these RJ proteins may act as competitive inhibitors for these viral 530 enzymes. In addition, this study examined the nsp7-nsp8 and nsp10 critical 531 binding residues in nsp12 and nsp16, respectively, using nsp12-nsp7-nsp8 and 532 nsp16-nsp10 complex templates (PDB: 7BV2 and 6YZ1, respectively). Data 533 revealed that MRJP2-but not MRJP2 X1-can interact with many of the nsp7-534 nsp8 and nsp10 binding residues. Therefore, the binding of MRJP2 to nsp12 or hypoxia and its pathogenesis, due to their ability to efficiently bind to most of 589 the oxy-and deoxyhemoglobin binding sites on the viral nsps. Therefore, MRJP2 and MRJP2 isoform X1 represent a hope of eliminating this deadly virus 591 that has been spreading at an alarming rate. The obtained results suggest specific potency and mechanisms for 593 each of these RJ proteins. In this context, the authors predict the use of both 133N, 135T, 137K, 138G, 139S, 140F,141L, 166E, 168P, 169T, 170G, 171V, 172H,190T, 191A, 192Q,193A, 194A, 195G, 196T, 197D, 199T, 204V, 236K, 237Y, 238N, 239Y 224T, 244Q, 247V, 254S, 255A, 258G, 259I, 260A, 261V, 262L, 263D. Oxy-hemoglobin-nsp9 complex -26.06 Chain A 78D, 79T, 80P, 107A, 108A, 109T, 110V, 111R. Chain Deoxyhemoglobin-nsp5 complex -42.09 Chain A 48D, 50L, 51N, 52P, 53N, 56D, 57L, 60R, 188R, 190T, 191A Chain B 154Y, 209Y, 212V, 213I, 217R,247V, 248D, 249I, 251G, 252P, 253L, 254S, 255A, 256Q, 257T, 258G, 294F, 297V, 301S, 302G. 19Q, 21T, 23G, 24T,25T, 26T, 27L, 46S, 47E, 49M, 69Q, 118Y, 119N, 142N , 143G, 189Q. Deoxyhemoglobin-nsp9 complex -26.59 102D, 103F, 108D, 110T, 111L, 112I, 113G,119H, 120T, 121A, 160K, 286N, 287R, 288V, 289V, 291S, 292S , 293D, 294V, 295L, 296V, 297N. Chain B (nsp10) 76Y, 80H, 81I, 82D, 83H, 86P, 87K, 88G, 89F, 90C, 93K. The blue, red, and orange colored residues referred to the amino acid residues in the nsp-MRJP2, nsp-MRJP2 X1, 864 or both, respectively that matched the binding site residues of nsp-hemoglobin complex. SARS-CoV-2, severe 865 acute respiratory syndrome-related coronavirus; nsps, non-structural proteins. Origin and evolution of pathogenic 650 coronaviruses Anti-leukemic Antiviral, antifibrotic and 655 anticancer activities of royal-jelly proteins. 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