After
the declaration of the Zika epidemic as an international public health
emergency by WHO in February 2016, research on Zika Virus (ZIKV) has increased
several folds. Previously, ZIKV, a mosquito borne virus, was considered to
induce only mild illness, but now it has been established as the cause of
severe clinical manifestations, including fetal anomalies, neurological
problems, and autoimmune disorders making infections with ZIKV a substantial
public health concern. Genomic and molecular investigations are ongoing to
investigate ZIKV pathology and enhanced pathogenicity, as well as to design
safe and potent vaccines, drugs, and therapeutics.
The
review article published in Frontiers in Microbiology journal,
compiled by authors from India, Mexico and USA, covers some recent therapies
and drug targets that have shown promise in inhibiting and countering ZIKV
infection, which includes limiting viral entry into cells, targeting the ZIKV
helicase protein, use of nucleoside analogs like 2′-C-methylated nucleosides
and 7-deaza-2′-C-methyladenosine to terminate nascent RNA strand formation,
host nucleoside biosynthesis inhibitors, NS2B-NS3 protease, small molecules,
methyltransferase inhibitors, covalent inhibitors of viral protein expression,
interferons, drugs designed with the aid of computers, neutralizing antibodies,
convalescent serum, antibodies that limit antibody-dependent enhancement,
anti-Toll-like receptor molecules and use of herbal drugs. Authors have
enlisted many FDA approved drugs which have been tested and can be repurposed
for treating ZIKV infection in humans. However, to date, no FDA category A drug
has been identified, which is clinically safe for use in mothers and fetuses.
While using monoclonal antibodies or vaccines, Antibody dependent enhancement
(ADE) is of major concern in the application of ZIKV therapies mainly in
geographical regions where other flaviviruses are endemic.
Thus,
to limit ADE, antibodies are being engineered to contain a modified Fc region.
Modification of the Fc region of antibodies not only hampers their attachment
to FcγRs to inhibit internalization of the immune complex, but also reduces
complement binding, and thereby preventing ADE. For engineered mAb, two
mutations i.e., LALA and N297A substitution have been identified, that prevent
internalization of immune complexes. In the future, several such mutations may
be recognized, and humanized mAbs can be genetically engineered to prevent ADE
as well as optimal efficacy. Combinatorial use of such engineered antibodies
might be evaluated for synergistic effects in other therapeutic and
prophylactic regimens. The information provided in this review article would
update the current knowledge as well as aid in designing and developing safe
and potent drugs, therapeutics and pharmaceuticals to curtain the ill effects
of ZIKV.
Journal
Reference:
Ashok
Munjal, Rekha Khandia, Kuldeep Dhama*, Swati Sachan, Kumaragurubaran Karthik,
Ruchi Tiwari, Yashpal S. Malik, Deepak Kumar, Raj K. Singh, Hafiz M. N. Iqbal
and Sunil K. Joshi. Advances in Developing Therapies to Combat Zika Virus:
Current Knowledge and Future Perspectives. Frontiers in Microbiology, 2017,
Volume 8, Article 1469, https://doi.org/10.3389/fmicb.2017.01469
Posted by Dr. Tim Sandle
