SUMMARYRecombinant and parental poliovirus particles were indistinguishable by ratezonal and isopycnic sedimentation, and by u.v. inactivation. Sensitive selective procedures, applied to ts + recombinants to detect genetic segregation of one parent, failed to reveal any. Poliovirus genetic recombinant particles thus appear to be conventional virus particles; their significance for recombination mechanisms is discussed. Sensitivity to the growth inhibitor 2-(3-chloro-p-tolyl)-5-ethyl-l,3,4-oxadiazole is shown to depend on a product of the structural protein gene.
The synthesis and antirhinovirus activity of syn and anti isomers of 6-[[(hydroxyimino)phenyl]methyl]-1-[(1-methylethyl)sulfonyl]-1H-benzimidazol-2-amine (4 and 5) are reported. The structural assignments of 4 and 5 are based upon 13C NMR spectra of both isomers and also X-ray analysis of 5. The anti-isomer 5 was more potent than the syn-isomer 4 when compared as an inhibitor of rhinovirus multiplication in vitro. Both isomers inhibited multiplication of 15 different serotypes of rhinovirus.
In the studies conducted, arginine deficiency suppressed herpes simplex virus replication in tissue culture. Lysine, an analog of arginine, as an antimetabolite, antagonized the viral growth-promoting action of arginine. The in vitro data may be the basis for the observation that patients prone to herpetic lesions and other related viral infections, particularly during periods of stress, should abstain from arginine excess and may also require supplemental lysine in their diet.
The compound 2-amino-1-(isopropyl sulfonyl)-6-benzimidazole phenyl ketone oxime (LY122771-72) at a concentration of 0.2 microgram/ml completely inhibited rhinovirus replication in human embryonic nasal organ cultures, although in the absence of virus the compound did not inhibit ciliary activity when used at a concentration of 25 micrograms/ml. When added 26 hr after infection, the compound stopped rhinovirus production in organ cultures that had already started to release virus. Five rhinovirus types available for infection of volunteers and six recently obtained clinical isolates were shown to be more sensitive to LY122771-72 in tissue culture than the rhinovirus type 31 used in the organ culture experiments. These results suggest that this potential antiviral drgu should be evaluated in humans.
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