Developing broad-spectrum antivirals to target many viruses at once

Humanity faces an essentially unlimited pool of virus threats. The emergence of new viruses like HIV, Ebola, or Zika is only going to increase as humans encroach further into the wild environment. The question is, what are scientists going to do about it? The major problem is that to develop a new drug or vaccine typically takes 10 years and costs on the order of a billion dollars, and the ones currently available only act on a highly specific target.

Paul Ahlquist, virology investigator at the Morgridge Institute for Research and HHMI investigator, says people are not nearly as safe against disease as they would like to think they are.

This serious imbalance - unlimited threats and limited responses - is not a winning game for humanity. We need to change this game."

Paul Ahlquist, virology investigator, Morgridge Institute for Research

At the Morgridge Institute, one of the highest priorities is to develop broad-spectrum antivirals. That is, to use the limited capacity and resources available to produce agents that will target many viruses at once and thereby get more bang for the investment in each case.

Broad-spectrum agents already exist to battle against bacteria. If a child scrapes a knee, an adult could go into the medicine cabinet and pull out a general antibiotic ointment that is typically a mixture of several things to protect the child. They don't have to start a gene-sequencing experiment to figure out what kind of bacteria might be in that scrape.

Solutions like that don't exist right now for viruses. Society needs something that might work against a great many different viruses at once.

One approach the Ahlquist lab is taking is to target the functions of the host cell, rather than the functions of the virus directly. Scientists have already identified over a hundred specific host genes that are involved in different steps of virus replication, as well as the pathways that a virus follows to deposit its infectious payload.

"As we analyze those pathways, we're finding that often many different viruses depend on a common pathway," Ahlquist says. "Viruses whose fundamental molecular biology are quite different can have a common vulnerability from this angle. We just need to figure out how to shut that street down."

As technologies have become more powerful, scientists can also go after all pathways in the cell to simply catalog the major needs of large numbers of viruses.

"We can do experiments now on the scale of tens of thousands of genes, something that was not possible when I started doing this work," Ahlquist says. "These are extremely valuable experiments that don't involve a pre-designed hypothesis. The viruses are winning, but in an environment that values fundamental research, we have a much better chance of shifting the balance in our direction."