NEW ORLEANS-Physicians have done better fighting death and taxes than they have battling the common cold.
But unlike death and taxes, the cold-a group of acute coryzal illnesses-only seems invincible. Studies of the structure and behavior of cold viruses are turning up potential preventives, possible ways to sidetrack replication, and sites vulnerable to antiviral agents, say reports at the Interscience Conference on Antimicrobial Agents and Chemotherapy here.
The goal is to defy Sir William Osler’s dictum that the only way to treat a cold is “with contempt.”
It won’t be easy. Members of five viral families, including coronaviruses, influenza and parainfluenza viruses, and 100 rhinoviruses, cause colds.
Coronavirus colds incubate a little longer and have a shorter duration than those due to rhinoviruses, but symptoms of both types are similar.
Many drugs are antirhinoviral in vitro but so far few have worked clinically, says Baylor microbiologist Robert Couch. Though antibodies to rhinoviruses develop in seven to 14 days and last for years, the multiplicity of serotypes and lack of crossreacting antigens are problems in all immunization approaches.
Colds affect nearly everyone, but some cold virus infections have a subclinical course. Billions are spent annually on cold remedies in the U.S. At Toronto’s Hospital for Sick Children, a survey found more than 800 OTC cold preparations.
In addition to a runny nose, sneezing, coughing, headache, a scratchy throat, fatigue, and myalgia, 10% to 20% of patients have fever. Dr. Jack Gwaltney Jr.’s University of Virginia team used CT to show that 90% of patients had sinus abnormalities. He thinks that suggests the common cold is actually “viral rhinosinusitis.”
Purdue virologist Michael G. Rossmann says rhinoviruses have vulnerabilities. They are nonenveloped single-stranded RNA. Though small, each consists of 60 asymmetric units containing four viral polypeptides. Three of the peptides form a shell and have puffs that are binding sites of neutralizing antibodies.
Rhinoviruses contain canyons that x-ray crystallography and electron microscopy indicate are the sites recognized by the cellular receptor molecules. Beneath each canyon is a pocket that is the binding site for hydrophobic compounds that can inhibit attachment and uncoating of the virus. Dr. Rossmann thinks that the investigational hydrophobic drug VP 63843, now called pleconaril (ViroPharma), will work against 80% of rhinoviruses.
In a double-blind trial of 33 volunteers inoculated intranasally with coxsackievirus A21, which binds to the same receptor site as a rhinovirus, those treated with VP 63843 had a mean symptom score of 1.0, vs. 7.4 for placebo controls, and 6% had fever, vs. 38% of controls, Dr. Gilbert Schiff of Cincinnati Children’s said here.
Therapy for colds, Dr. Gwaltney says, calls for a two-pronged approach to knock out the virus and relieve symptoms from the host’s response. He says intranasal interferon a2b and ipratropium, plus oral naproxen, significantly reduced symptoms of experimentally induced rhinoviral colds.
Cold viruses may turn out to be vulnerable to specific protease inhibitors. Dr. Arlene Collins of SUNY Buffalo and Lund University’s Dr. Anders Grubb have found that low-molecular-weight human cysteine-protease inhibitors, cystatin C and D included, block the replication of coronaviruses in vitro. Dr. Grubb’s Swedish team has cloned some of the 11 known human cystatins, nine of which are low-molecular-weight.
Investigational imiquimod (Aldara, 3M), an interferon-
inducer, protected rats from airway dysfunction during acute viral infection, says the University of Wisconsin’s Dr. Jeffrey Stokes. This IF- inducer is aimed at treating genital warts.
A nasal spray with ICAM-1 (intracellular adhesion molecule-1) that prevented rhinovirus infection in chimps is in preclinical testing. Bayer researcher Edward Huguenel says soluble ICAM-1 acts as a decoy and prevents viruses from binding to the cellular receptors.
Zinc can reduce a cold’s duration, according to Dr. Michael Macknin of the Cleveland Clinic. His team studied 100 clinic employees who sucked a lozenge containing zinc gluconate or a placebo every two hours within 24 hours of developing a cold. The zinc recipients’ colds lasted a median 4.4 days, vs. 7.6 days for 50 controls. Wayne State’s Dr. Ananda Prasad says the improvement is most likely antiviral. Zinc has helped in three of seven studies.
Steam therapy for colds was supposed to make nasal passages too hot for the viruses to replicate, but results of clinical trials varied. The now-defunct British Common Cold Unit reported steam reduced symptoms 80%, but Cleveland Clinic and University of Virginia studies showed no therapeutic effect.
Antibiotics, though firmly contraindicated, were prescribed in 33% of 17 million visits for URIs, says the CDC’s Dr. Scott Dowell. Physicians often say they prescribe antibiotics so a cold won’t progress to a bacterial infection. But Dr. Gwaltney says that rarely occurs in adults’ colds and it would take a huge study to determine whether antibiotics prevent pediatric colds from progressing.
A frequent cold Rx is “take two aspirins and call me in the morning,” and chicken soup, which is said to improve mucociliary clearance, is a favorite adjuvant therapy. Chicken soup’s counterpart south of the Mason-Dixon line, say some authorities, is bourbon. -Elsie Rosner
NEW ORLEANS-Physicians have done better fighting death and taxes than they have battling the common cold.
