Human respiratory syncytial virus (RSV) is a single-stranded, negative-sense RNA virus belonging to the Paramyxoviridae family. Unfortunately, RSV usually causes childhood acute lower respiratory infection and produces severe disease at any age. Infants, the elderly, as well as those having compromised cardiac, pulmonary, or immune systems are particularly vulnerable.

The primary site of RSV replication in the human respiratory tract is the cytoplasm of epithelial cells, which comprise the pseudostratified lining of the bronchial airway.

RSV exists as two antigenic subgroups: A and B. PC786 demonstrates profound inhibition of both RSV A and B strain replication. PC786 is a novel non-nucleoside low MW RSV polymerase inhibitor. The effects of PC786 against a panel of viruses are evaluated. In addition, PC786 produces potent, concentration-dependent inhibition of viral replication. PC786 also shows inhibitory activities against RSV-induced increases of CCL5, IL‐6, double-strand DNA, and mucin. However, PC786 does not inhibit CXCL8.

Recently, PC786 has been optimized for topical inhalation treatment. Once-daily treatment with PC786 on days -1 to 3, by either intratracheal (i.t.) or intranasal (i.n.) administration, was found to inhibit viral loads in the lungs of RSV A2-infected BALB/c mice.

All in all, a topically administered, highly potent, low MW inhibitor targeting the replication complex of RSV is a promising candidate for the treatment of RSV infection. Hopefully, the Development of PC786 is underway.

Reference:

Br J Pharmacol. 2018 Jun;175(12):2520-2534.