CONTACT INACTIVATION OF RNA AND DNA VIRUSES BY N‐METHYL ISATIN BETA‐THIOSEMICARBAZONE AND CuSO₄*

The Thiosemicarbazones

“…The inactivation kinetics of neurovaccinia and rabbitpox over a lO-h period at 37°C in the presence of 40 J!M IBT (a ten-fold lower concentration would inhibit poxvirus growth by over 90% in cells derived from embryonic rabbit kidney; SHEFFIELD 1962) were identical. This type of result has been repeatedly confirmed (EASTER-BROOK 1962;ZGORNIAK-NoWOSIELSKA et al 1973;Fox et al 1977), even though contact inactivation of vaccinia and rabbitpox virus by MIBT occurs in the presence of exogenously added CuS0 4 (Fox et al 1977). The latter is a provocative finding because vaccinia contains copper; at least, it has not been eliminated from virus preparations as purification techniques have improved (HOAGLAND et al 1941;JOKLIK 1962;ZWARTOUW 1964).…”

“…Furthermore, CUS04 alone (even 1,000 times its effective concentration when combined with MIBT) had no ability to cause trapping of nucleic acid. Other results (Fox et al 1977) with Sindbis virus and poliovirus also indicated that the possession of virion-associated enzymes was not a prerequisite for contact inactivation and would lend support to the Levinson hypothesis.…”

“…Such chelating agents as Tris buffer or histidine (in tissue culture media), when present with IBTs, will prevent inactivation of her- LEVINSON and HELLING (1976) pesvirus . The remaining viruses that have been examined (LOGAN et al 1975;Fox et al 1977) are inactivated by IBTs very slowly unless exogenous CUS04 is supplied. Invariably, inactivation proceeds faster in phosphatebuffered saline than in tissue culture medium.…”

“…Thus, LEVINSON et al (1973 b) considered that MIBT acted as a scavenger (for trace contamination from glassware or media) and vehicle to transport copper to an appropriate site. Parenthetically, CuS04 alone (or elemental copper in the case of influenza virus) has been found to inactivate on contact herpesvirus , rabies virus (Fox et al 1977), Sindbis virus (Fox et al 1977), and influenza virus (ONG 1958). After inactivation, Rous sarcoma virus was shown still to retain its ability to adsorb to cells .…”

Inhibition of Moloney Leukaemia Virus Production by N-methylisatin-beta-4':4'-diethylthiosemicarbazone

“…The drug was reported to cause a contact inactivation of Moloney sarcoma virus (MSV) and other viruses (Levy et al 1976;Fox et al It has previously been shown that isatin-fl-thiosemicarbazone (IBT) compounds varied in their effect on the growth and DNA synthesis of animal cells (Sadler,x965). We found that treatment with I7/ZM-IBDET suppressed DNA synthesis after I h, while I7/z~-M-IBDET caused 50% inhibition only after 6 h. Some of the isatin-fl-thiosemicarbazone derivatives are reversible inhibitors of cellular DNA synthesis.…”