Systems, methods, computer readable media and articles of manufacture consistent with innovations herein are directed to computer virtualization, computer security and/or memory access. According to some illustrative implementations, innovations herein may utilize and/or involve a separation kernel hypervisor which may include the use of a guest operating system virtual machine protection domain, a virtualization assistance layer, and/or a instruction execution detection/interception mechanism (which may be proximate in temporal and/or spatial locality to malicious code, but isolated from it). The instruction execution detection/interception mechanism may perform processing, inter alia, for detection and/or notification of, and actions upon by a monitoring guest, code execution by a monitored guest involving predetermined physical memory locations, such as API calls. Such actions may include interception of API calls within the monitored guest and simulation thereof by the monitoring guest or another authorized guest.