key: cord-0761940-plrlpyk9 authors: Kandeel, Mahmoud; Al‐Taher, Abdulla; Park, Byoung Kwon; Kwon, Hyung‐Joo; Al‐Nazawi, Mohammed title: A pilot study of the antiviral activity of anionic and cationic polyamidoamine dendrimers against the Middle East respiratory syndrome coronavirus date: 2020-05-08 journal: J Med Virol DOI: 10.1002/jmv.25928 sha: dc4e4ee20954b6635e768b4b35d2c4e4e7a89839 doc_id: 761940 cord_uid: plrlpyk9 The Middle East respiratory syndrome coronavirus (MERS‐CoV) is an emerging virus that causes infection with a potentially fatal outcome. Dendrimers are highly branched molecules that can be added to antiviral preparations to improve their delivery, as well as their intrinsic antiviral activity. Studies on identifying anti‐MERS‐CoV agents are few. Three types of polyanionic dendrimers comprising the terminal groups sodium carboxylate (generations 1.5, 2.5, 3.5, and 4.5), hydroxyl (generations 2, 3, 4, and 5), and succinamic acid (generations 2, 3, 4, and 5) and polycationic dendrimers containing primary amine (generations 2, 3, 4, and 5) were used to assess their antiviral activity with the MERS‐CoV plaque inhibition assay. The hydroxyl polyanionic set showed a 17.36% to 29.75% decrease in MERS‐CoV plaque formation. The most potent inhibition of MERS‐CoV plaque formation was seen by G(1.5)‐16COONa (40.5% inhibition), followed by G(5)‐128SA (39.77% inhibition). In contrast, the cationic dendrimers were cytotoxic to Vero cells. Polyanionic dendrimers can be added to antiviral preparations to improve the delivery of antivirals, as well as the intrinsic antiviral activity. The Middle East respiratory syndrome coronavirus (MERS-CoV) is a major health hazard in several countries. 1 Like the severe acute respiratory system (SARS)-CoV, the MERS-CoV is transferred to humans from animal sources. 2 The MERS-CoV was found to be transferred within human families, so that it caused a communicable disease. 3 The disease was initially found on the Arabian peninsula and it then spread to several countries around the world. 4 Dendrimers are highly branched structures with repetitive sequences of monomers called dendrons. Dendrimers have three main components: (a) a core moiety, (b) branching units, and (c) surface groups. 5 The diameter of a dendrimer is nanosized, similar to certain globular proteins. For instance, the G4 polyamidoamine (PAMAM) dendrimer has a diameter of 4 nm, which is identical to the diameter of cytochrome c. The diameter of the G5 PAMAM is 5 nm, like that of hemoglobin. Therefore, dendrimers are considered to be biomimetics of synthesized proteins, but they have significantly better stability (protease resistance); more lack of complex beta-sheets, coils, and loops of proteins; and a better intrinsic ability to bind drugs through their well-defined internal cavities and surface functions. 6 Dendrimers have unique structural features 7 : (a) their sizes vary from less than 2 nm to more than 10 nm, according to the number The plaque reduction assay was performed as reported previously. 14 We thank the central labs at King Faisal University for facilities. No animals/humans were used for the studies that are basis of this study. 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