1. Introduction A novel human coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that emerged in Wuhan, China, in December 2019, has reached a pandemic level of global incidence [1]. The virus can enter the human body through the eyes, mouth, or nose and replicate itself after binding to receptors in the lung and other organs. Studies indicate the SARS-CoV-2 virus can remain viable and infectious suspended in aerosols for hours and on surfaces up to days, enabling efficient aerosol and fomite transmission of SARS-CoV-2 [2,3,4,5,6]. A recent study showed that 6 feet may not be sufficient to protect against coronaviruses, which may travel up in droplets up to 27 feet, but it was received with skepticism [7]. A single sneeze may emit 40,000 droplets with a geometric mean size of 360.1 µm exhaled immediately at the mouth [8]. Over 87% of particles exhaled by flu influenza patients were under 1 µm [9]. However, a similar percentage was reported for significantly larger (0.3–0.5 mm) particles exhaled by subjects infected with rhinovirus [10]. A computational model created by Vuorinen et al. [11] within a multi-institutional project shows that a cough from a person in one aisle in a grocery store spreads as a cloud of nanosized particles over the shelves into the next aisle. Similar open-source simulations can be found on the internet for cough aerosols spreading over aisles in an airplane. Earlier studies indicate that human movement in an airplane cabin increases the risk of infections by reducing the overall deposition and removal rate of the suspended aerosols [12]. Hospitals and clinics follow rigorous guidelines to maintain hygiene at 35–60% relative humidity (RH) and 21–24 °C temperature values (NFPA 99), with a mandated six air exchanges per hour (6 ACH). The role of ventilation in removing exhaled bioaerosols in buildings to prevent cross infections has been extensively studied after the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak in 2003 and can help inform mitigation strategies for the current SARS-CoV-2 pandemic [13]. Swabs taken from the air exhaust outlets in a hospital tested positive for SARS-CoV-2, suggesting that small virus-laden droplets may be transported by airflows and deposited on vents [4]. Due to the limitations of the sampler used in the study, the virus was not detected in the airflow. A scientific study of aerosol particles in a cruise ship’s heating, ventilation and air conditioning system found no detectable SARS-CoV-2 transmission, on surfaces or in the air [14]. However, a combined dose–response modeling study indicates the potential for airborne transmission [15]. Viable coronavirus (SARS-CoV-2) found on the Diamond Princess Cruise ship surfaces weeks after people were evacuated indicates that the virus survives for longer times on surfaces and forms biofilm-like structures, which may be influenced by environmental conditions [16]. Recent studies reveal that poor air quality and atmospheric pollution may be linked to the spread of the virus resulting in a greater number of COVID-19 cases in polluted areas [17]. Despite the increasing number of studies, there are still many unknowns about how SARS-CoV-2 spreads indoors and its infectability. The objective of this study was to gain more knowledge about the effect of environmental factors on the transport and viability of virus aerosols in the built environment based on computational airflow modeling and virus aerosol collection using the wetted wall cyclone samplers developed in the aerosol technology laboratory where this study was conducted. As ventilation systems are practically ubiquitous in common workplaces, the effect of air properties on the infectivity and transport of aerosolized viruses is one of the most important subjects for study to aide in reducing the spread of infectious viral particles. This study is one of the first comprehensive studies on the impact of environmental conditions including temperature, relative humidity, and air velocity on the transport, and deposition of airborne viruses. The identification of effective environmental conditions and development of optimized ventilation designs could significantly reduce the entrainment and spread of viable infectious viruses in the air. The authors’ previous work indicates that a combined modeling and sampling approach can be used to mitigate transport of airborne infectious microorganisms in a ventilated facility [18]. Based on the airflow model and the bioaerosol movement, an optimal air intake/exhaust design can be selected that would result in the highest sanitation requirement (i.e., the least number of infectious agents) in the airflow. This study addresses the need for an optimal air intake/exhaust design combined with optimal environmental conditions to reduce the amount of SARS-CoV-2 viral particles in the air by integrating aerobiology with particle tracking and computational fluid modeling. Ultimately, this work allows for a better understanding of the behavior of virus size particles and a redesign for ventilation systems for reduced virus transmission at facilities, with a potential for application to any built environment. The outcome of this study has the potential to protect public health through continuous monitoring of viral concentrations, with sufficient throughput to detect dynamic changes in concentration levels in room-size spaces. The potential for efficient detection of viable virus aerosols and mitigation of their spread was assessed by conducting controlled experimental studies to establish the pattern for aerosolization, deposition, and resuspension of SARS-CoV-2 simulant viruses at different environmental conditions and modeling the airflow pattern in a model hospital room to determine the effect of ventilation on the entrainment and spread of virus aerosols.