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Genomic Modeling as an Approach to Identify Surrogates for Use in Experimental Validation of SARS-CoV-2 and HuNoV
Brahmaiah Pendyala1, Ankit Patras1, Bharat Pokharel1
1Department of Agricultural and Environmental Sciences, Food Science Program, College of Agriculture, Tennessee State University, Nashville, TN, United States.
Abstract:
Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) is responsible for the COVID-19 pandemic that continues to pose significant public health concerns. While research to deliver vaccines and antivirals are being pursued, various effective technologies to control its environmental spread are also being targeted. Ultraviolet light (UV-C) technologies are effective against a broad spectrum of microorganisms when used even on large surface areas. In this study, we developed a pyrimidine dinucleotide frequency based genomic model to predict the sensitivity of select enveloped and non-enveloped viruses to UV-C treatments in order to identify potential SARS-CoV-2 and human norovirus surrogates. The results revealed that this model was best fitted using linear regression with r 2 = 0.90. The predicted UV-C sensitivity (D 90 - dose for 90% inactivation) for SARS-CoV-2 and MERS-CoV was found to be 21.5 and 28 J/m2, respectively (with an estimated 18 J/m2 obtained from published experimental data for SARS-CoV-1), suggesting that coronaviruses are highly sensitive to UV-C light compared to other ssRNA viruses used in this modeling study. Murine hepatitis virus (MHV) A59 strain with a D 90 of 21 J/m2 close to that of SARS-CoV-2 was identified as a suitable surrogate to validate SARS-CoV-2 inactivation by UV-C treatment. Furthermore, the non-enveloped human noroviruses (HuNoVs), had predicted D 90 values of 69.1, 89, and 77.6 J/m2 for genogroups GI, GII, and GIV, respectively. Murine norovirus (MNV-1) of GV with a D 90 = 100 J/m2 was identified as a potential conservative surrogate for UV-C inactivation of these HuNoVs. This study provides useful insights for the identification of potential non-pathogenic (to humans) surrogates to understand inactivation kinetics and their use in experimental validation of UV-C disinfection systems. This approach can be used to narrow the number of surrogates used in testing UV-C inactivation of other human and animal ssRNA viral pathogens for experimental validation that can save cost, labor and time.
Insights
A new genomic model predicts virus sensitivity to UV-C light, identifying Murine hepatitis virus as a SARS-CoV-2 surrogate. This aids in developing effective UV-C disinfection strategies for controlling viral spread.
Area of Science:
- Virology and Microbiology
- Environmental Health Engineering
- Genomic Modeling
Background:
- The COVID-19 pandemic caused by SARS-CoV-2 highlights the need for effective environmental disinfection technologies.
- Ultraviolet germicidal irradiation (UV-C) is a promising technology for inactivating a wide range of viruses.
- Identifying suitable viral surrogates is crucial for experimentally validating UV-C disinfection efficacy.
Purpose of the Study:
- To develop a genomic model predicting virus sensitivity to UV-C light.
- To identify potential non-pathogenic surrogates for SARS-CoV-2 and human noroviruses (HuNoVs) for UV-C inactivation studies.
- To provide insights for optimizing UV-C disinfection validation.
Main Methods:
- Developed a pyrimidine dinucleotide frequency-based genomic model to predict UV-C sensitivity (D90).
- Utilized linear regression (r² = 0.90) to fit the model.
- Predicted UV-C sensitivity for SARS-CoV-2, MERS-CoV, and various HuNoV genogroups, identifying potential surrogates like MHV and MNV-1.
Main Results:
- Coronaviruses (SARS-CoV-2, MERS-CoV) showed high sensitivity to UV-C light (D90 values of 21.5 and 28 J/m², respectively).
- Murine hepatitis virus (MHV) A59 (D90 = 21 J/m²) was identified as a suitable surrogate for SARS-CoV-2.
- Human noroviruses (HuNoVs) exhibited lower sensitivity (D90 = 69.1–89 J/m²), with Murine norovirus (MNV-1) (D90 = 100 J/m²) proposed as a conservative surrogate.
Conclusions:
- The genomic model effectively predicts viral UV-C sensitivity, aiding in surrogate selection.
- SARS-CoV-2 and HuNoVs have distinct UV-C inactivation profiles, necessitating specific surrogates for validation.
- This approach can streamline and reduce the cost and time of validating UV-C disinfection systems for various viral pathogens.

