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Zika Virus (ZIKV) belongs to the class of flavivirus that can be transmitted by Aedes mosquitoes. The number of Zika virus caused cases of acute infections, neurological disorders and congenital microcephaly are rapidly growing and therefore, in 2016, the World Health Organization declared a global “Public Health Emergency of International Concern”. Anti-ZIKV therapeutic and vaccine development strategies are growing worldwide in recent years, however, no specific and safe treatment is available till date to save the human life. Currently, development of peptide therapeutics against ZIKV has attracted rising attention on account of their high safety concern and low development cost, in comparison to small therapeutic molecules and antibody-based anti-viral drugs. In present review, an overview of ZIKV inhibition by peptide-based inhibitors including E-protein derived peptides, antimicrobial peptides, frog skin peptides and probiotic peptides has been discussed. Peptides inhibitors have also been reported to act against NS5, NS2B-NS3 protease and proteasome in order to inhibit ZIKV infection. Recent advances in peptide-based therapeutics and vaccine have been reviewed and their future promise against ZIKV infections has been explored.

Our previous study showed that YGGFMKKKFMRFamide (YFa), a chimeric peptide of Met-enkephalin, and Phe-Met-Arg-Phe-NH2 induced naloxone-reversible antinociception and attenuated the development of tolerance to morphine analgesia. In continuation, the present study investigated which specific opioid receptors-mu, delta or kappa-mediate the observed YFa antinociception pharmacologically using specific antagonists and whether chronic administration of YFa at 26.01 micromol/kg per day induces tolerance and its effect on the expression of mu and kappa opioid receptors from day 4 to day 6, with endomorphine-1 (EM-1) and saline taken as positive and negative controls, respectively. Quantitative differential expression analysis was carried out by real-time reverse-transcriptase polymerase chain reaction, and the corresponding changes in protein levels were assessed by Western blot. A pharmacological investigation revealed that nor-binaltorphimine, a specific kappa opioid receptor-1 (KOR1) antagonist, completely antagonized the antinociception induced by 39.01 micromol/kg of YFa. Importantly, its chronic intraperitoneal administration did not result in significant tolerance over 6 days, whereas EM-1 induced significant tolerance after day 4. Differential expression analysis revealed that EM-1 caused up-regulation of mu opioid receptor-1 on day 4, followed by down-regulation on later days. Interestingly, YFa treatment caused a decrease on day 4, followed by an increase in the expression of KOR1 from day 5 onward. In conclusion, YFa induces kappa-specific antinociception, with no development of tolerance during 6 days of chronic treatment, which further articulates new directions for improved designing of peptide-based analgesics that may be devoid of adverse effects like tolerance.

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