Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

Abstract

The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host’s immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host’s innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of the pattern recognition protein (PRP) trident composed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.

Commentary: Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

“…These two studies focused on the fragment rfhSP-D rather than the full length rhSP-D. The study by Arroyo et al is consistent with the body of evidence discussed by Labarrere and Kassab ( 1 ), documenting the role of full length rhSP-D promoting viral aggregation and clearance.…”

“…Labarrere and Kassab recently wrote an informative paper that includes a very interesting overview of the role Surfactant Protein D (SP-D) plays as part of the innate immune system in the defense against several viral pathogens including SARS-CoV-2 ( 1 ). It has been described that the Carbohydrate Recognition Domain (CRD) of SP-D recognizes and binds to carbohydrates present in certain viruses such as the hemagglutinin of Influenza A Virus ( 2 , 3 ) or the Spike (S)-Protein of SARS-CoV and SARS-Cov-2 ( 4 , 5 ).…”

Response: Commentary: Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

“…Thus, there is a continued need for therapies that can be used early in the disease course to reduce the risk of disease progression, prevent transmission, and be widely distributed to meet global demand” ( 8 ). The rapid emergence of new SARS-CoV-2 variants ( 9 , 10 ) with adaptive mutations in the spike protein can result in the persistence of the disease and certainly make necessary the use of a “multiple weaponry method” ( 2 ) to more effectively be able to reduce or perhaps eliminate the COVID-19 disease.…”

“…Vaccines, neutralizing monoclonal antibodies, immune modulators, and antivirals are primary components of the treatment armamentarium ( 2 , 8 ). Using dodecameric SP-D, SP-D inhibitory receptors ( 2 ), virus removal by other pattern recognition proteins [SP-A, pentameric C-reactive protein, innate immunoglobulin M (IgM) natural antibodies, Toll-like receptor inhibitors, and others] will facilitate reduction of lung disease severity in particular ( Figure 1 ), and COVID-19 disease in general.…”

“…We appreciate their comments about our article being informative and interesting and for making emphasis on the importance of innate immunity and particularly SP-D in the defense against multiple viral pathogens including SARS-CoV-2 ( 1 ). As noted, numerous studies highlighted the value of high serum SP-D levels upon development of severe COVID-19 disease ( 1 , 2 ). As correctly pointed out, deficient pulmonary SP-D levels have been reported in severe COVID-19 and have been associated with increased risk of acute respiratory distress syndrome ( 1 , 3 , 4 ) and were also found in several chronic pulmonary diseases ( 5 ).…”