Format

Send to

Choose Destination
Drug Discov Ther. 2019;13(6):314-321. doi: 10.5582/ddt.2019.01084.

Inhibitions of human parainfluenza virus type 2 replication by ribavirin and mycophenolate mofetil are restored by guanosine and S-(4-nitrobenzyl)-6-thioinosine.

Author information

1
Microbiology and Immunology Section, Department of Clinical Nutrition, Graduate School of Health Science, Suzuka University of Medical Science, Suzuka, Mie, Japan.
2
Department of Clinical Nutrition, Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie, Japan.
3
Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, Japan.
4
Department of Microbiology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
5
Graduate School of Mie Prefectural College of Nursing, Tsu, Mie, Japan.

Abstract

The antiviral activities of a nucleoside analog antiviral drug (ribavirin) and a non-nucleoside drug (mycophenolate mofetil) against human parainfluenza virus type 2 (hPIV-2) were investigated, and the restoration of the inhibition by guanosine and S-(4-nitrobenzyl)-6-thioinosine (NBTI: equilibrative nucleoside transporter 1 inhibitor) were also investigated. Ribavirin (RBV) and mycophenolate mofetil (MMF) inhibited cell fusion induced by hPIV-2. Both RBV and MMF considerably reduced the number of viruses released from the cells. Virus genome synthesis was inhibited by RBV and MMF as determined by polymerase chain reaction (PCR) and real time PCR. mRNA syntheses were also reduced. An indirect immunofluorescence study showed that RBV and MMF largely inhibited viral protein syntheses. Using a recombinant green fluorescence protein (GFP)-expressing hPIV-2 without matrix protein (rhPIV-2ΔMGFP), it was found that virus entry into the cells and multinucleated giant cell formation were almost completely blocked by RBV and MMF. RBV and MMF did not disrupt actin microfilaments or microtubules. Both guanosine and NBTI completely or partially reversed the inhibition by RBV and MMF in the viral replication, syntheses of genome RNA, mRNA and protein, and multinucleated giant cell formation. NBTI caused a little damage in actin microfilaments, but had no effect on microtubules. Both RBV and MMF inhibited the replication of hPIV-2, mainly by inhibiting viral genome RNA, mRNA and protein syntheses. The inhibition was almost completely recovered by guanosine. These results indicate that the major mechanism of the inhibition is the depletion of intracellular GTP pools.

KEYWORDS:

Human respiratory tract pathogen; a recombinant green fluorescence protein expressing hPIV-2 without matrix protein; antiviral drug; mycophenolic acid; recovery of virus replication inhibition

PMID:
31956229
DOI:
10.5582/ddt.2019.01084
Free full text

Supplemental Content

Full text links

Icon for J-STAGE, Japan Science and Technology Information Aggregator, Electronic
Loading ...
Support Center